tbuckley/cabot-search huggingface dataset:
Abstract 9782: Sudden Death in U.S. College Athletes: Incidence, Causes, and Implications for Preparticipation Screening
Authors: Barry J Maron, Tammy S Haas, Caleb J Murphy, Aneesha Ahluwalia, Stephanie Rutten-Ramos
Journal: Circulation (2013)

Introduction: Frequency with which cardiovascular-related sudden deaths (SD) occur in competitive athletes importantly impacts considerations for the most appropriate preparticipation screening strategy, particularly the potential value of incorporating the12-lead ECG. Hypothesis: Unsuspected cardiovascular disease may not be the predominant cause of sudden death in college athletes. Methods: We assessed databases (including autopsy reports) from both the U.S. National Sudden Death in Young Athletes Registry and National Collegiate Athletic Association (NCAA) (2002-2011) to define the incidence and causes of SD in college student-athletes. Results: Over the 10 year period, 182 SDs occurred (ages 20 ± 1.7; 85% males; 64% white): 52 resulting from suicide (n = 31) or drug abuse (n = 21), and 64 probably or likely attributable to cardiovascular causes. Of the 64 athletes, 47 had a confirmed post-mortem diagnosis, most commonly hypertrophic cardiomyopathy in 21, and congenital coronary anomalies in 8. The 4,052,369 athlete participations (in 30 sports over 10 years) incurred mortality risks of: suicide and drugs combined, 1.3/100,000 athlete participation-years (5 deaths/year); documented cardiovascular disease, 1.2/100,000 (4 deaths/year); and cardiovascular diseases judged reliably detectable by screening ECGs, 0.7/100,000 (2-3/year). Notably, cardiovascular deaths were significantly (5-fold) more common in African-American athletes than whites (3.8 vs. 0.7 100,000; p &lt;0.01), but were less frequent in NCAA college athletes than in the general population of the same age (p &lt; 0.01). Conclusions: In college student-athletes, SD risk due to cardiovascular disease is relatively low, with mortality rates similar to that of suicide and drug abuse, significantly less than expected in the general population, but highest in African-Americans. About 40% of confirmed cardiovascular deaths may not have been reliably detected by preparticipation screening, even with 12-lead ECGs.
Abstract 9543: βArrestin1 Genetic Deletion Improves Cardiac Function and Adverse Remodeling in Heart Failure
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Ashley Siryk, Samalia Dabul, Erhe Gao, Walter J Koch
Journal: Circulation (2013)

Introduction: Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, including catecholamines and aldosterone, which contribute to the increased morbidity and mortality associated with myocardial infarction (MI). Cardiac ß-adrenergic receptor (AR) desensitization is a hallmark molecular abnormality in HFand is due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the ßarrestins (ßarrs). We have also recently established that ßarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression. Hypothesis: Herein, we sought to investigate the effects of genetic deletion of ßarr1 on post-MI cardiac function and structure in mice progressing to HF. Methods: We utilized the global ßarr1 knockout (KO) mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/Bl6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma hormones were measured by ELISA. Adverse remodeling markers` mRNA expression was assessed by real time PCR. Results: Cardiac function is markedly improved in ßarr1KO`s at 4 weeks post-MI compared to WT mice (ejection fraction: 41.5±2.8% vs. 21.8±2.4%, respectively, n=9, p&lt;0.0001). Isoproterenol-induced contractility is also enhanced. Additionally, cardiac dimensions are significantly reduced compared to WT`s, as are levels of adverse remodeling markers, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone and catecholamine levels are significantly lowered and cardiac ßAR signaling and function appear elevated in post-MI ßarr1KO`s compared to control WT`s. Conclusions: Genetic deletion of ßarr1 substantially improves cardiac function, adverse remodeling, neurohormonal status and ßAR function during post-MI HF progression. The underlying mechanism appears to be attenuation of both cardiac ßAR desensitization and adrenal cardiotoxic hormone production, both ßarr1-dependent phenomena.
Abstract 338: Therapeutic Hypothermia for Patients With Post-Resuscitation Shock After Out-of-Hospital Cardiac Arrest
Authors: Taketomo Soga, Ken Nagao, Hiroyuki Yokoyama, Naohiro Yonemoto, Hiroshi Nonogi
Journal: Circulation (2013)

Background: Animal data have suggested a beneficial effect of therapeutic hypothermia following return of spontaneous circulation (ROSC) (post-ROSC cooling) in cardiogenic shock, but there are few human studies of patients with post-resuscitation shock who were treated with post-ROSC cooling. METHODS: From the J-PULSE HYPO registry, a multi-center registry in Japan, we selected the patients who met the following inclusion criteria: bystander-witnessed cardiac arrest due to ventricular fibrillation (VF), target core temperature of 32-34°C, and cooling duration of 12-72 hours. Study patients were divided into two groups based on hemodynamic status. The post-resuscitation shock group consisted of patients with systolic blood pressure &lt; 90 mmHg and/or mechanical circulation support. The remaining patients constituted the non-shock group. The primary endpoint was favorable neurological outcome at 30 days after cardiac arrest. Results: Of the 452 adult patients treated with post-ROSC cooling, 292 met the inclusion criteria; 149 (51%) were post-resuscitation shock and 143 (49%) were non-shock. No significant difference was observed between the two groups in the frequency of 30-day favorable neurological outcome (63% [94/149] post-resuscitation shock group vs. 68% [97/143] non-shock group; p=0.39). However, the median collapse-to-ROSC interval was significantly longer in the post-resuscitation shock group than in the non-shock group (27 minutes vs. 20 minutes, p&lt;0.001). In the quartiles of collapse-to-ROSC interval and 30-day favorable neurological outcome, both groups exhibited high frequencies of 30-day favorable neurological outcome in Quartile 1, in which the collapse to ROSC interval was 15 minutes or less (93% post-resuscitation shock group vs. 87% non-shock group, p=0.40), and a significant decrease in 30-day favorable neurological outcome was found in each group as the quartile value of collapse-to-ROSC interval increased (p&lt;0.001, respectively). The 30-day favorable neurological outcome in each Quartile 2, 3 and 4 did not differ between the two groups. Conclusion: Due to the effects of post-ROSC cooling, post-resuscitation shock patients were able to achieve the same level of neurological benefit as non-shock patients.
Abstract 9629: Cathepsin K-Mediated Noich1 Activation Contributes to Neovascularization in Response to Hypoxia
Authors: Lina Hu, Xian Wu Cheng, Guo-Ping Shi, Haiying Jang, Aiko Inoue, Yumiko Yamamura, Hongxian Wu, Kyosuke Takeshita, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya
Journal: Circulation (2013)

Background: Cysteine proteases play important roles in human pathobiology. This report shows the participation of cathepsin K (CatK) in ischemia-induced neovascularisation. Methods and Results: Left femoral artery ligation-induced ischemia in mice showed increased CatK expression and activity. CatK-deficient young and aged mice showed impaired functional recovery following hind ischemia. These mice also showed reduced levels of cleaved Notch1 (c-Notch1), vascular endothelial growth factor (VEGF), Flt-1 and phospho-Akt proteins of the ischemic muscles. In vitro , CatK knockdown reduced the levels of c-Notch1, VEGF and Flt1, essential molecules for angiogenesis and vasculogenesis. Together, the effects of CatK knockdown led to defective endothelial cell invasion, proliferation and tube formation. Recombinant human CatK degrades gama-secretase substrate in time- and dose dependent manners, suggesting CatK is involved in Notch1 activation. This was reinforced by the finding that CatK inhibition impairs Notch1 activation in response to hypoxia with no change in known gama-secretase activity.CatK-deficiency decreased circulating EPC-like CD31+/c-Kit+cells in mice of both ages. Transplantation of bone-marrow-derived mononuclear cells from CatK+/+ mice restored neovascularisation in CatK -/- mice. Conclusions: CatK activity controls neovascularisation via partial modulation of Notch1 signaling activation in response to hypoxia. Thus, CatK has a critical role in vascular formation and represents a new therapeutic target for vascular disease.
Abstract 9894: Rho-associated Kinase Activity and Cardiovascular Disease Prediction
Authors: Masato Kajikawa, Tatsuya Maruhashi, Yumiko Iwamoto, Takeshi Matsumoto, Akimichi Iwamoto, Takayuki Hidaka, Yasuki Kihara, Kensuke Noma, Ayumu Nakashima, James K Liao, Yukihito Higashi
Journal: Circulation (2013)

Background: Cardiovascular diseases are associated with chronic activation of Rho-associated kinase. Rho-associated kinase activity is significantly correlated with endothelial function and Framingham risk score, but there is no information on the prognostic value on Rho-associated kinase activity. Methods: We evaluated Rho-associated kinase activity in peripheral leukocytes by Western blot analysis in 633 subjects who underwent health-screening examination at Hiroshima University Hospital. We assessed the associations between Rho-associated kinase activity and first major cardiovascular events (death from cardiovascular causes, myocardial infarction, and stroke), death from cardiovascular causes, acute myocardial infarction, stroke, revascularization (percutaneous coronary intervention, coronary artery bypass grafting) and hospitalization for heart failure. Results: During a median period of 42.0 months (interquartile range, 24.4 to 56.6 months) of follow-up, 29 subjects died (10 from cardiovascular causes), 2 myocardial infarction, 20 revascularization, 15 stroke, and 17 hospitalization for heart failure. After adjustment for age, sex, cardiovascular risk factors and other relevant variables, Rho-associated kinase activity remained a strong independent indicator of first major cardiovascular events (hazard ratio, 2.19; 95 percent confidence interval, 1.35 to 3.70; P=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95 percent confidence interval, 1.18 to 6.60; P=0.002), stroke (hazard ratio, 2.14; 95 percent confidence interval, 1.24 to 3.86; P=0.006) and revascularization (hazard ratio, 2.68; 95 percent confidence interval, 1.60 to 4.66; P&lt;0.001). Conclusions: Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of leukocyte Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.
Abstract 9803: Optimization and Comparison of Myocardial T1 Techniques at 3T in Patients With Aortic Stenosis
Authors: Calvin W Chin, Scott Semple, Tamir Malley, Audrey White, Saeed Mirsadraee, Peter Weale, Sanjay Prasad, David E Newby, Marc R Dweck
Journal: Circulation (2013)

BACKGROUND: T1 mapping is an emerging cardiac magnetic resonance imaging technique to assess diffuse myocardial fibrosis. However, the optimal approach remains uncertain, especially at 3T. We sought to optimize and compare the most widely-used techniques. METHODS: T1 mapping was performed at 3T using the modified-look-locker-inversion sequence in 20 healthy volunteers and 20 patients with aortic stenosis (AS). Pre- and post-contrast myocardial T1, the partition coefficient (λ) and interstitial contrast volume of distribution (Vd) were assessed. After establishing the optimal time-point and myocardial region for analysis, we compared the reproducibility of these T1 measures and their ability to differentiate asymptomatic patients with AS from healthy volunteers. RESULTS: There was no segmental variation across the ventricle in any of the T1 measures evaluated. λ and Vd did not vary with time, while post-contrast T1 was relatively constant between 15-30min. Thus, mid-cavity myocardium at 20min was used for subsequent analyses. Vd displayed excellent intra-, inter-observer, and scan-rescan reproducibility (intra-class correlation coefficients (ICC) 1.00, 0.97 and 0.96 respectively), as did λ (ICC 0.99, 0.94, 0.93 respectively). Moreover, Vd and λ were both higher in patients with AS compared to controls (Vd 28.3±1.7 versus 26.0±1.6%, p &lt;0.001; λ 0.46±0.03 versus 0.44±0.03, p =0.02) (Figure 1A). By comparison, scan-rescan reproducibilities for pre- and post-contrast myocardial T1 values were only modest (ICC 0.72 and 0.56) with no differences observed between cases and controls (both p&gt;0.05) (Figure 1B). CONCLUSIONS: We recommend Vd and λ to assess diffuse myocardial fibrosis at 3T based upon their superior reproducibility and ability to identify disease states.
Abstract 259: Available Prehospital Covariates Predict Coronary Ischemia as the Cause of Sudden Out-of-Hospital Cardiac Arrest Among Failed Resuscitations
Authors: Sydney Hartsell, Daryl McLaren, Martin de la Presa, Peter Taillac, Scott T Youngquist
Journal: Circulation (2013)

Introduction: Intra-arrest percutaneous coronary intervention (PCI) has been proposed to increase survivorship from sudden out-of-hospital cardiac arrest (OHCA) that fails prehospital resuscitation. Given costs and system constraints to intra-arrest PCI, the ability to predict coronary ischemia as the cause of arrest may be beneficial to guide its performance. HYPOTHESIS: We hypothesized that readily available prehospital information would predict coronary ischemia as the cause of OHCA amongst failed resuscitation attempts. METHODS: Review of medical examiner reports for adult victims of OHCA for whom prehospital resuscitation was attempted. Data was linked to prehospital data documenting Utstein variables and patient demographics. Logistic regression was performed to generate a predictive model for coronary ischemia as the cause of arrest. Results: 119 autopsy reports were identified. Of these, 68 (57%) were terminated in the field, 51 (43%) in the ED. Males composed 77% of the sample. Mean age was 50+14 years. Coronary ischemia was determined to be causative in 50/119 (40%) of failed arrests. A logistic regression model that included shockable rhythm (OR 13, 95% CI 4-47), age (OR 2 per decade of life, 95% CI 2-4), and male gender (OR 6, 95% CI 1-32) demonstrated an area under the receiver-operating curve of 0.88 and correctly classified 76% of cases. Predictive probabilities derived from the model can be used to predict individual risk (Figure). CONCLUSIONS: In conclusion, the combination of an initial shockable rhythm, advanced age, and male gender are all highly predictive of acute coronary ischemia as the cause of OHCA.
Abstract 9249: Percutaneous Closure versus Medical Therapy for Cryptogenic Stroke in Patients With a Patent Foramen Ovale: A Meta-Analysis of Randomized Controlled Trials
Authors: Christopher Pickett, Todd Villines, Michael Ferguson, Edward Hulten
Journal: Circulation (2013)

Objectives: To systematically review and perform a meta-analysis of randomized controlled trials(RCT) comparing percutaneous closure of patent foramen ovale(PFO) to medical therapy in patients with cryptogenic stroke or transient ischemic attack(TIA). Background: Up to 61% of patients with cryptogenic stroke under the age of 55 years have been found to have a PFO. Observational studies have demonstrated reductions in recurrent, neurologic events with PFO closure compared to medical therapy. Recent RCT have shown non-significant trends toward benefit. Methods: We systematically searched for RCT of percutaneous PFO closure versus antiplatelet or anticoagulation medical therapy in patients with cryptogenic stroke or TIA and performed a meta-analysis of treatment outcomes. The primary end point was combined death, stroke, or TIA as defined by each study. Results: Three RCT of 2303 patients were included. In all, 1150 patients underwent PFO closure and 1153 received medical therapy and were followed over a median of 2.6(2.0-4.1) years. The pooled incidence of the primary end point was 1.2(95% confidence interval:0.2-2.3) events/100 patient-years in the PFO closure group and 1.8(0.7-2.9) in the medical therapy group(p=0.32), with a number needed to treat(NNT) of 167(100-500). The corresponding pooled hazard ratio(HR) was 0.67(0.44-1.01,p=0.054) in favor of PFO closure. PFO closure was associated with an increased incidence of atrial fibrillation, relative risk =3.51(1.44-8.55,p=0.006). When stratified by device, the Amplatzer™ showed a significant stroke prevention benefit, HR=0.44(0.21-0.95,p=0.037). Conclusions: In comparison to medical therapy alone, PFO closure trends toward decreased hazard of combined events, although the absolute event reduction is small with a high NNT in the population studied.
Abstract 19093: Paradoxical Improvement of Tricuspid Valve Incompetence Severity Following Implantation of Ventricular Leads
Authors: Giselle A Baquero, Javier E Banchs, Pradeep Yadav, Soraya M Samii, Erica Penny-Peterson, Deborah L Wolbrette, Gerald V Naccarelli, Mario D Gonzalez
Journal: Circulation (2013)

Background: Cardiac rhythm management devices (CRMD) require an endocardial ventricular lead to be placed across the tricuspid valve. Worsening tricuspid regurgitation (TR) with implantation of CRMD has been described. We report the incidence of improvement in TR after CRMD placement, which is an unexpected finding. Methods: We retrospectively reviewed 148 patients (age 68±15) that received a CRMD. TR, ejection fraction (EF) and pulmonary artery systolic pressure (PASP) measured by Doppler echocardiography before and after CRMD implantation were analyzed. The TR was graded according to the degree of severity as mild, moderate and severe. A scale of 0-4 according to the grade of severity was used. Improvement in the severity of TR was classified corresponding with the reduction in grades of severity of TR as follows: minimal (&lt;1grade), slight (1), and significant reduction (≥2). Results: Mean follow-up time was 30±12 months. Thirty-nine (26%) patients experienced improvement in the severity of TR (from 1.7±0.8 to 0.9±0.7; p=0.0001-5) after placement of a CRMD. The remaining 109 patients had an increase in the severity of TR (from 0.1±0.5 to 1.4±0.9; p=0.0005-10). Reduction in TR was associated with improvement in EF (from 41±19 to 47±14%; p=0.01) and PASP (from 45±15 to 36±14mmHg; p=0.002-2). Patients that had increase in TR did not have a significant change in their EF (from 40±17 to 42±15%; p=0.07) and had worsening of their PASP (from 38±14 to 42±16mmHg; p=0.002). Evaluation of improvement in TR per type of device implanted revealed no difference between patients who received pacemakers (PPM), defibrillators (ICD) or cardiac resynchronization therapy devices (CRT) (ICD/CRT vs PPM p=0.12; ICD vs PPM p=0.22; ICD vs CRT p=0.29 and CRT vs PPM p=0.07). Conclusion: Severity of TR may improve in some patients after CRMD placement. This could be attributed to diuresis and optimization of medical therapy at the time of CRM implant or restoration of AV synchrony with pacing, as evidenced by the reduction in PASP and improved EF among those patients.
Abstract 9565: Left Atrial “Reservoir” and “Passive Emptying” Reserve During Dobutamine Stress Have Prognostic Relevance for Patients With Dilated Cardiomyopathy
Authors: Kensuke Matsumoto, Hidekazu Tanaka, Kazuhiro Tatsumi, Yoshiki Yamadori, Takuma Sawa, Yasuhide Mochizuki, Tatsuya Miyoshi, Yoshiki Motoji, Yuko Fukuda, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2013)

Background: Left atrial (LA) structural and functional remodeling has been proposed as a predictor of cardiovascular outcomes. However, the importance of LA functional reserve for patients with depressed left ventricular (LV) function remains unclear. The objective of this study was thus to test the hypothesis that diminished augmentation of LA function during dobutamine stress may be associated with adverse cardiovascular events in patients with dilated cardiomyopathy (DCM). Methods: Sixty-seven DCM patients with ejection fractions of 35±9% were recruited, and LA strain was determined as the averaged global speckle-tracking longitudinal strain from apical 4- and 2-chamber views during dobutamine stress (20μg/kg/min). The systolic component of LA strain (S-LAs) was considered to reflect reservoir function, whereas the passive (S-LApass) and active emptying components (S-LAa) were considered to reflect conduit and booster-pump function, respectively. Event-free survival was tracked over a 17-month period. Results: Both relative increases in the LA reservoir (cut-off ≤10.9%; 71% sensitivity and 89% specificity, p&lt;0.001) and in passive emptying function(cut-off ≤12.3%; 93% sensitivity and 85% specificity, p&lt;0.001) during dobutamine stress were significantly predictive of adverse cardiovascular events. The patients with good LA “reservoir reserve” (ΔS-LAs &gt;24.7% [median]) and “passive emptying reserve” (ΔS-LApass &gt;32.5% [median]) had a significantly better prognosis than those with poor functional reserve (log rank p&lt;0.001, respectively). Of particular importance was that the absence of “reservoir reserve” and “passive emptying reserve” was associated with the worst outcome (event rate: 90.0%), whereas the reverse condition was associated with the lowest adverse event rate (2.4%; p&lt;0.001). Conclusions: Diminished augmentation of LA reservoir and passive emptying function is closely associated with adverse cardiovascular event.