tbuckley/cabot-search huggingface dataset:
Abstract 12486: An Early Survey of the Incidence and Distribution of LVAD Thrombus Using a High-avidity Tc-99m Fibrin Probe
Authors: Michael Nassif, Grace Cui, Walter J Akers, Michael J Scott, Akinobu Itoh, Krishna Paranandi, Samuel Achilefu, Gregory A Ewald, Gregory M Lanza
Journal: Circulation (2015)

Background: 99mTc-F4A is a tetrameric, fibrin-specific probe characterized in vitro, in mice and in left ventricular assist devices (LVAD) explanted from patients. Objective: To survey the incidence and spatial distribution of thrombus by 99mTc-F4A signal intensity in LVADs removed for pump exchange (n=9) or heart transplant (n=11) in an early cohort of patients. Methods: LVADs excised from patients were rewired and operated (~9,400 RPM) in a mock circulatory loop (1/2 tygon, 200ml, 50:50, PBS: plasma; heparin). 99mTc-F4A (500μCi) was injected into the loop, circulated for 30 min. Activity was localized within LVADs by NanoSPECT/CT. Results: The median time of LVAD support prior to explant was 7.6 ± 7.2 months. Thrombus was detected in 19/20 LVADs by high 99mTc-F4A signal and corroborated by gross pathology in 4 LVADs by the manufacturer. 99mTc-F4A signal was scored as strong, weak, or none, and was assessed for the inlet cannula (metallic and Gor-Tex tubing segments), the inlet stator/bearing, turbine, outlet bearing, and outlet cannula regions. Inlet cannulas were available for 8/20 LVADs with 7/8 having thrombus. Strong signal was noted in 4/7 of the metallic segment and in 5/7 of the Gor-Tex segments. 99mTc-F4A signal occurred around the inlet bearing in 8/20 LVADs and the outlet bearing region in 5/20 LVADs, but the incidence of thrombus within the axial turbine was negligible. Thrombus was observed in the outlet cannula in 10/20 pumps. (Fig) Strong 99mTc-F4A signal was noted most often at the inlet bearing 75% (6/8) and in outlet cannulas 50% (5/10). Strong signal was noted in 13/20 LVADs in at least one location. Of 5/20 LVADs with multiple deposits, 4/5 of these pumps had a strong 99mTc-F4A signal. Conclusion: These initial ex vivo survey data reveal a high incidence of LVAD thrombus in exchanged and routinely transplanted LVADs. 99mTc-F4A imaging may offer a sensitive and specific diagnostic tool to noninvasively assess and better manage LVAD thrombus.
Abstract 18524: Left Atrial Function is Associated With Cardiopulmonary Performance in Heart Failure With Preserved Ejection Fraction: A Relax Substudy
Authors: Ravi V Shah, Siddique A Abbasi, Steven McNulty, Adrian Hernandez, Tomas G Neilan, Phillip G Haines, Mark Semigran, Barry A Borlaug, Gregory Lewis, Michael Jerosch-Herold, Raymond J Kim, Margaret Redfield, Raymond Y Kwong
Journal: Circulation (2013)

Introduction: Impaired left atrial (LA) function may limit optimal cardiac performance, reflecting both LA load and atrial dysfunction in HFpEF. The link between MRI-derived LA characteristics and exercise capacity in HFpEF has not been studied. Hypothesis: We hypothesized that total LA emptying fraction (LAEF) is reduced in HFpEF vs. healthy controls and LA functional impairment would be correlated with LV diastolic dysfunction, vascular dysfunction, and exercise intolerance. As LA hypertension may increase right ventricular load and limit increases in pulmonary perfusion with exercise, the correlation of LAEF with ventilatory efficiency (VE/VCO2 slope) was also examined. Methods: Baseline exercise, echo, and cardiac MRI data from RELAX (a study of sildenafil in HFpEF) in patients in sinus rhythm with a measureable LAEF by MRI (n=100) were utilized. Healthy volunteers (n=21) were included for comparison. LAV was measured by the biplane area-length method using 2-/4-chamber SSFP CMR. LAEF was defined as total (ΔLAVmax-min), passive/conduit (ΔLAVmax-before atrial contraction ), and active (ΔLAVbefore atrial contraction-min), each divided by maximal LAV. Results: As compared to controls, LAEF (particularly passive conduit function) was reduced in HFpEF (Table 1). In HFpEF, patients with lower LAEF had a larger LA, more echo diastolic dysfunction, higher PA systolic pressure and NT-proBNP, reduced aortic distensibility, worse exercise capacity, and ventilatory inefficiency (Table 2). Conclusions: LA function is impaired in HFpEF, may serve as a marker of chronic LA hypertension and may contribute to impaired exercise intolerance and ventilatory inefficiency.
Abstract 12225: Effects of Obesity on Noninvasive Testing and Angiography Results in Patients With Suspected Cardiac Ischemia: Insights From the PROMISE Trial
Authors: Sheldon Litwin, Adrian Coles, Neha J Pagidipati, Kerry L Lee, Patricia A Pellikka, Daniel B Mark, James E Udelson, Udo Hoffmann, Pamela S Douglas
Journal: Circulation (2016)

Background: Evaluation of obese patients with suspected CAD is challenging because obesity is a CV risk factor, but adiposity itself may mimic symptoms of CAD and reduce the accuracy of diagnostic testing. Optimal testing strategies in obese patients are not known. Methods: Patients with stable symptoms suggestive of cardiac ischemia from the PROMISE trial (n=9230) were classified according to BMI. Providers specified a functional test modality prior to stratified randomization to functional (stress testing) or anatomical (CTA) testing. We assessed relationships between BMI, physician’s preference of functional test, test positivity and results of catheter angiography (cath) using logistic regression. Results: Providers were more likely to choose SPECT over other functional tests as BMI increased (OR 1.04 per unit increase in BMI above 27, p&lt;0.001). In patients with BMI ≥ 35 vs. &lt; 35, the rate of positivity with CTA was similar (10% vs. 12%; see Table). The same was true for stress echo and stress ECG (positivity 8-13%, p&gt;0.8 for both). In contrast, SPECT was significantly more likely to be positive in those with BMI ≥ 35 vs. &lt;35 (18% vs. 13%; p=0.001). The likelihood of finding obstructive CAD at cath did not differ with BMI ≥ 35 vs. &lt;35 in patients having CTA (59% vs. 52%, p=0.22), but among SPECT patients, positivity was only 29% with BMI ≥ 35 compared to 52% with BMI &lt; 35 (p=0.005; Table). Conclusions: Increasing levels of obesity were associated with stronger physician preference for SPECT over other noninvasive tests. In patients receiving SPECT, higher levels of obesity were associated with a higher rate of positive results, but a lower cath yield for obstructive CAD. In contrast, in patients receiving CTA, positivity rates and cath yield did not vary by BMI. Obesity appears to significantly influence provider decision-making with regard to noninvasive test choice, probability of abnormal test results and probability of finding obstructive disease at cath.
Abstract 12117: Screening for Metabolic Risk in Adolescent Blood Donors
Authors: Stephen Eason, Odette Gore, Colby Ayers, Shankar Goudar, Merlyn H Sayers
Journal: Circulation (2015)

Introduction: Cardiometabolic risk factors such as elevated blood pressure, total cholesterol and glycated hemoglobin (HbA1C) in adolescents persist into adulthood and are associated with increased risk for cardiovascular disease and diabetes. These risks are increased when multiple risk factors are present. High school blood drives are a unique opportunity to provide screening for cardiometabolic risk factors at low cost and minimum inconvenience to participants. Methods: Blood pressure (SBP and DPB), total nonfasting cholesterol and HbA1C were measured in volunteer blood donors aged 16-19 years, donating blood between January 2011 and December 2012, through Carter BloodCare in Dallas/Fort Worth, Texas. Cardiometabolic risk factors were classified as elevated (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg, cholesterol ≥ 200 mg/dL, HbA1C ≥ 6.5%) and borderline or elevated (SBP ≥ 120 mmHg and/or DBP ≥ 80 mmHg, cholesterol ≥ 170 mg/dL, HbA1C ≥ 5.7%). Results: The study included 24,925 donors (11,590 boys and 13,335 girls), including 8.4% African American, 2.2% Asian, 52.7% Caucasian, 24.9% Hispanic and 11.8% other/unknown. Only 33.6% of the entire cohort had no borderline or elevated risk factors (Table). However, 41.6% of females and 51.8% of males had at least 1 borderline or elevated risk factor. When viewed by ethnicity, 48.2% of Caucasians and 45.1% of African Americans had 1 borderline or elevated risk factor, with almost 25 % of African Americans having 2 or more borderline or elevated risk factors. Conclusions: Blood donor screening is confirmed as an opportunity to monitor the prevalence of multiple metabolic risk factors in an ostensibly healthy subset of the population. This scrutiny does identify individuals with multiple risk factors and also reveals ethnic and gender differences.
Abstract 18490: The Use of a Personalized Gene Expression Score in Women Presenting to Primary Care With Symptoms of Suspected Obstructive Coronary Artery Disease Improves Clinical Decision Making Around Non-Invasive Diagnostic Testing: Gender-Specific Results From the IMPACT-PCP (Investigation of a Molecular Personalized Coronary Gene Expression Test on Primary Care Practice Pattern) Trial
Authors: Lee Herman, James Froelich, Dino Kanelos, Robert St Amant, May Yau, Brian Rhees, Mark Monane, John McPherson
Journal: Circulation (2013)

Introduction: Better methods are needed to evaluate symptomatic patients with suspected obstructive coronary artery disease (CAD), particularly among women as current methods overestimate disease prevalence. A previously validated blood-based diagnostic test with a negative predictive value of 96% among patients with low gene expression score (GES ≤ 15) uses expression levels of 23 genes to determine the likelihood of a patient having at least one vessel with ≥50% coronary artery stenosis. Use of a GES early in the diagnostic work-up for obstructive CAD may impact quality and efficiency of care. Hypothesis: In this gender-based analysis, we hypothesized that GES results would lead to a change in the clinician’s diagnostic assessment of women presenting with symptoms suggestive of obstructive CAD. Methods: The IMPACT-PCP Trial ( NCT01594411 ) evaluated 251 consecutive patients with no prior history of CAD who presented to nine primary care clinicians for evaluation of chest pain and related symptoms and underwent GES testing. The clinicians outlined their diagnostic strategy before and after GES results were known. The primary outcome was the decision change in the diagnostic strategy pre/post GES testing as measured by regression modeling. In this pre-specified secondary analysis, we focused on the assessment of women in this prospective cohort. Results: There were 140 women (56%) eligible for analysis, with mean age 59 years (SD± 13). Mean GES was 11 (SD± 9), with 76% (n=107) of women patient with low GES. Following GES, a change in the evaluation plan was noted in 83 patients (59% observed vs 10% expected change, p&lt;0.001). More patients had a decreased (n=69, 49%) vs increased (n=14, 10%) intensity of testing (p&lt;0.001). In particular, 96% (66/69) of patients with decreased testing had low GES (≤ 15), while 93% (13/14) of patients with increased testing had elevated GES. There has been one MACE event reported (judged as not related to CAD status by the clinician) over 30 days of follow-up. Conclusions: The GES showed clinical utility in the evaluation of suspected obstructive CAD by affecting clinical decision making among primary care practitioners and was associated with an overall relevant reduction in diagnostic test utilization among women with low GES.
Abstract 12471: CHA <sub>2</sub> DS <sub>2</sub> VASc Score Predicts Future Development of Atrial Fibrillation After Successful Catheter Ablation of Typical Atrial–Flutter
Authors: Adarsh Bhan, Paula Dunskis, Jeffrey S Neiger, Christopher Blair, Manoj Duggal
Journal: Circulation (2016)

Introduction: After successful catheter ablation (CA) for typical atrial flutter (AFL), long term development of atrial fibrillation (AF) is common. No definitive predictive models currently exist to identify patients who are likely to develop AF. The aim of this study was to evaluate whether CHA 2 DS 2 VASc score can predict future occurrence of AF after successful CA of AFL. Methods: We conducted a retrospective chart review of 171 consecutive patients with isolated AFL who underwent successful CA between years 2007-2014 at a teaching community hospital. Patients with at least 2 years of follow-up were included for analysis. 40 patients were lost to follow-up. CHA 2 DS 2 VASc scores were calculated at the time of CA. Follow up consisted of in-office electrocardiograms, and (when available) in-office and remote device interrogation. Patients were anticoagulated at the discretion of their treating physician. The endpoint was time to first occurrence of AF. Data was analyzed using appropriate descriptive and univariate statistics to describe, compare and contrast based upon AF occurrence groups. A cox regression was performed to examine CHA 2 DS 2 VASc score as a predictor of AF occurrence during CA follow-up. Results: 131 patients were included in the study. Average age was 66 ±11.5 years and follow-up duration was 26.6±1.5 months. AF occurred in 52 patients (39.7%) by 2 years. Patients who developed AF had a CHA 2 DS 2 VASc score of 3.4±1.4, compared to 2.6±1.3 for patients who did not (p &lt; 0.003). Patients who developed AF were also older (70.2±10.3 vs. 63.7±11.6 years, p&lt;.001,), and had a higher rate of Hypertension (3.40±1.35 vs. 2.6±1.3, p=.037,). CHA 2 DS 2 VASc score was found to be significantly associated with AF onset during the 2 year follow-up (p&lt;.007, Hazard Ratio 1.36, 95%CI 1.09-1.70). Conclusion: The incidence of AF following CA of AFL is common. CHA 2 DS 2 VASc score may be a useful tool and predictor of AF after typical AFL ablation. This needs to be evaluated further in larger randomized trials which may help in guiding long term anticoagulation therapy.
Abstract 18464: Prognostic Value of Cardiac I-123 Metaiodobenzylguanidine Imaging in Patients With Chronic Heart Failure: A Prospective Comparative Study With Fragmented QRS Complexes
Authors: Satoshi Takahashi, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamamoto, Tsutomu Kawai, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Circulation (2013)

Backgrounds: Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with chronic heart failure (CHF). On the other hand, fragmented QRS complexes (fQRS) on the 12-lead ECG, which would be thought to reflect myocardial fibrosis, have been associated with poor outcome in CHF patients. However, there is no information available on the comparison of the prognostic values between MIBG imaging and fQRS in CHF patients. Methods: We studied 111 CHF outpatients with LVEF &lt;40% in our prospective cohort study. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate (WR) were calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as &gt; 27%. fQRS was defined by the presence of &gt;2 notches on the R wave or the S wave and had to be present in &gt;or=2 contiguous inferior (II, III, aVF), lateral (I, aVL, V(6)) or anterior (V(1) to V(5)) leads. Results: During a follow up period of 7.8±4.4 yrs, 39 patients had cardiac death. At multivariate Cox analysis, WR (p=0.0002) and LVEF (p=0.0035) were significantly independently associated with cardiac death, while H/M at the delayed image (p=0.003) and fQRS (p=0.088) showed the association with cardiac death at univariate analysis. Patients with abnormal WR (&gt;27%) had a significantly higher risk of cardiac death than those with normal WR (55% (31/56) vs 15% (8/55), p&lt;0.0001, adjusted hazard ratio 4.1 (95%CI 1.8-9.7)), while there was a tendency of higher risk of cardiac death in patients with fQRS (63%(10/16) vs 31%(29/95), p=0.08, hazard ratio 1.9 (95%CI 0.9-3.9)). Conclusion: The cardiac MIBG imaging had more valuable prognostic value than fQRS in CHF patients.
Abstract 12159: Metabolite Profiles Are Associated With Metabolically Unhealthy Obesity in Children and Adolescents
Authors: Aferdita Spahillari, Sarah de Ferranti, Stavroula Osganian, Michael E Pacold, Ravi V Shah, Venkatesh L Murthy
Journal: Circulation (2016)

Background: Metabolite profiling has been used to identify mechanisms of cardiometabolic disease (CMD). Whether metabolites can identify metabolic healthy obesity (MHO) versus unhealthy obesity (MUO) remains unclear. Hypothesis: We hypothesized that specific metabolite profiles would be associated with adverse cardiometabolic phenotypes in non-diabetic overweight/obese youth. Methods: We performed untargeted metabolomics (81 polar metabolites) in 90 overweight/obese youth (age 15.5±4.8 years, 54% female, BMI 33.8±10.0 kg/m 2 ), and used principal components analysis to identify metabolite clusters. Metabolically unhealthy obesity (MUO) was defined as one of the following: homeostatic model of insulin resistance (HOMA-IR) ≥ 3.16, hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg), triglycerides ≥ 150 mg/dl, HDL &lt;40 mg/dl or glucose ≥100. We used logistic regression to estimate the association between metabolite clusters and MUO. Results: Five principal components (PC) accounted for 61.9% variance in polar metabolites. Polar PC2 contained aromatic amino acids (phenylalanine, tyrosine), branched-chain amino acids (e.g., leucine, valine, isoleucine), and their downstream metabolites (e.g., glutamine) and was associated with MUO (odds ratio OR=1.92, 95% confidence interval CI 1.06-3.48, P=0.03). Conclusions: We identified patterns of metabolites previously implicated in diabetes risk in adults (e.g., branched chain and aromatic amino acids) associated with CMD phenotypes in overweight/obese youth. Common metabolic pathways contribute to heterogeneity in cardiometabolic health in pediatric obesity as in adults.
Abstract 18514: Rottlerin Greatly Improves Cardiac Functional Recovery Following Ischemic Cardioplegic Arrest (CP) in Wild-Type but Not BKCa Channel Knockout Mice
Authors: Brenda Cordeiro, Frank W Sellke, Richard T Clements
Journal: Circulation (2013)

Introduction: Mitochondrial BKCa channels are thought to provide protection during ischemic insults in the heart. Rottlerin, has been implicated as a potent BKCa activator, however this has not been firmly established. The purpose of this study was twofold: 1) investigate the efficacy of BKCa channel activation as a cardioprotective agent during cardioplegia/reperfusion (CP/R) and 2) assess the specificity of rottlerin for BKCa channels. Methods: Wt and BKCa KO mice were subjected to an isolated heart model of CP/R. Hearts were perfused for 30 min at 37C (baseline), followed by intermittent cold hypoxic CP with or without rottlerin (St Thomas II, 10C), and normoxic 37C reperfusion for 30 min. Mechanism of rottlerin-induced cardioprotection was also investigated using H9c2 cells subjected to in vitro CP/reoxygenation and assessed for mitochondrial membrane potential (TMRE) and ROS (DCFDA) production. Results: CP/R decreased LVDP (61.6 +/- 6 % baseline, n=6 ), +/- dP/dt (76.6+/- 7.3, 63.4 +/-7.7, % baseline respectively) and coronary flow (CF) (69.6+/-6.0 % baseline) in wt mice. Rottlerin, (100 nM (n=3), 500 nM (n=6)) dose dependently increased the recovery of LV function and CF to near baseline levels (% baseline 500 nM rottlerin, LVDP: 87.6+/- 4.0, +/-dPdt: 97.6 +/- 5.9, 90.9+/- 6.6, and CF: 125.3 +/-22.8, all p&lt;.01 vs CP ). BKCa KO hearts treated with (n=7) or without (n=7) 500nM rottlerin, were similar to wt CP hearts (% baseline BKCa KO + 500 nM rott: LVDP: 66.9+/- 6.0, +/-dP/dt 73.0 +/-3.6, 65.2+/- 4.2, and CF: 94.1 +/- 9.0). H9c2 cells subjected to in vitro CP/R, displayed reduced mitochondrial membrane potential (39 +/-.09 % decrease) and increased ROS generation (50+/-.04% increase), both of which were significantly (p&lt;.01) normalized by rottlerin (100 nM-1 uM) (n=8). Conclusions: Activation of BKCa channels profoundly rescues ischemic damage associated with CP/R, likely via effects on improved mitochondrial membrane potential and reduced ROS generation.
Abstract 18531: Adrenergic Stimulation Enhances Mitochondrial Ca <sup>2</sup> + Uptake and Cell Death Signaling Through Pyk2-Dependent Tyrosine Phosphorylation of the Mitochondrial Ca <sup>2</sup> + Uniporter
Authors: Jin O-Uchi, Bong Sook Jhun, Stephen Hurst, Anna Raffaello, Alina Ainbinder, Robert T Dirksen, Jianxin Sun, Rosario Rizzuto, Shey-Shing Sheu
Journal: Circulation (2013)

Introduction: Mitochondrial Ca 2+ homeostasis is crucial for balancing cell survival and death. The recent breakthrough discovery of the molecular identity of the mitochondrial Ca 2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study the role of mitochondrial Ca 2+ regulation in cardiac cells. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca 2+ entry through post-translational modifications of MCU are completely unknown. Hypothesis: Persistent adrenergic signaling induces mitochondrial Ca 2+ overload and activates cell death signaling through MCU tyrosine phosphorylation. Methods: Tyrosine kinase activation and tyrosine phosphorylation of MCU were observed in rat neonatal cardiomyocytes and H9C2 cardiac myoblasts. Mitochondrial Ca 2+ and reactive oxygen species (ROS) were measured using mitochondrial matrix-targeted Ca 2+ -sensitive inverse pericam and MitoSOX, respectively. Mitochondrial permeability transition pore (mPTP) activity was observed by monitoring the release of GFP-tagged mitochondrial protein, Smac-GFP, using confocal microscopy. Results: α 1 -adrenoceptor (α 1 -AR) signaling activates mitochondria-localized Ca 2+ -dependent tyrosine kinase named proline-rich tyrosine kinase 2 (Pyk2) and accelerates mitochondrial Ca 2+ uptake via Pyk2-dependent MCU phosphorylation and tetrametric MCU channel pore formation. Moreover, persistent α 1 -AR stimulation increases ROS production, mPTP activity, and initiates apoptotic signaling via Pyk2-dependent MCU activation and mitochondrial Ca 2+ overload. Moreover, pretreatment of a potent Pyk2 inhibitor PF-431396 or overexpression of dominant-negative mutant of MCU effectively inhibited α 1 -AR-mediated ROS generation and mPTP activation. Conclusion: The α 1 -AR-Pyk2 dependent tyrosine phosphorylation of the MCU regulates mitochondrial Ca 2+ entry and apoptosis in cardiac cells. Pyk2-MCU signaling may become novel potent therapeutic targets for preventing mitochondrial Ca 2+ overload, oxidative stress and cardiac injury under pathophysiological states such as heart failure, where catecholamine levels highly increase.