tbuckley/cabot-search huggingface dataset:
Abstract 19229: Effect of Blood Pressure Control on Mortality in Patients With Hypertension - Using the VA National Database
Authors: Ross D Fletcher, Raya Kheirbek, Richard L. Amdur L Amdur, Ronald E Jones, Charles Faselis, Vasalios Papademetrious
Journal: Circulation (2013)

Medical centers are being presented with an increasing number of hypertensives, and controlling Blood Pressure (BP) has become a healthcare imperative. The outcome of this control can be measured by analysis of mortality. The VA has used an Electronic Health Record with reminders since 1998 to detect and manage hypertension. Vital signs from the entire VA database were analyzed between 2001 and August 2011. Of 8,868,500 patients, 4,353,382 had elevations &gt;140 systolic or &gt;90 on three separate days. BP control was divided into patients who were controlled &gt;66%, 66 to 33%, and &lt;33% of the time. Mortality improvement varied with age. The mortality decreased in patients with 66% control compared to those with 33% control. This decreased mortality was 10.4% points for those under 70 years old, 13.4% points for 70 - 90 years old, and only .8% for those over 90. The % died was compared between patients with hypertension and those without hypertension in different age groups. The age groups were ≤ 50, 50 - &lt;60, 60 - &lt;70, 70 - &lt;80, 80 - &lt;90 and ≥90. The % point difference between groups and % increase in mortality for patients with hypertension in the ages ≤ 50 was 6.5 - 175%, 50 - &lt;60 was 4.2 - 28%, 60 - &lt;70 was 5.1 - 24%, 70 - &lt;80 was 1.7 - 3.5%, 80 - &lt;90 was .3 - .4%, and for those ≥90 minus .3 - minus .5%. Thus difference in mortality in hypertensive and normotensive groups decreases in higher age groups to the point where a slightly higher percent die in patients without hypertension than with hypertension in patients over 90. Control of BP over time is associated with decreased mortality in all age groups less than 90. After 90 control of BP has very little effect on mortality. Mortality in hypertensive patients is more than in normotensive patients until 90. When mortality is higher for patients with hypertension than those without, control of hypertension decreases mortality.
Abstract 19207: Outcomes in Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting With a Low-moderate Cha2ds2vasc Score. Do They Need Anticoagulation?
Authors: Albert Alonso, Antonia Sambola, Maria Mutuberria, Bruno Garcia, Jose A. Barrabes, David Garcia Dorado
Journal: Circulation (2013)

Background: European Society of Cardiology guidelines for the management of atrial fibrillation (AF) recommend oral anticoagulation (OAC) in patients with CHA2DS2VASc score ≥1. When in these patients a coronary stent (CS) is implanted, indication to dual antiplatelet therapy (DAPT) is added, so these patients may be receiving triple therapy (TT). Objective: We assessed the impact of TT in patients with non-valvular AF and a low-moderate thromboembolic risk (CHA2DS2VASc &lt; 2) submitted to coronary stenting (CS). Methods: a retrospective multicenter study was conducted from 2007 to 2011 to identify patients with nonvalvular AF who undergoing PCI with stenting. Patients clinical and demographic characteristics,CHADS2VASC2 score, PCI details, antithrombotic therapy at discharge and its duration. Follow-up was 1 year. Clinical outcomes were obtained from hospital readmissions and/or outpatients clinic interview were also reviewed. All bleeding events, stroke, thromboemobolism, death, acute myocardial infarction or target revascularization were recorded. Results: We identified 640 consecutive patients with nonv-valvular AF (75.2% male, 73.2±8.2 years). Of them 170 (27%) had a CHA2DS2VASc 3 (7.6% vs 4.2%; p=0.29). At follow-up, patients on TT showed a higher mortality (1.3% vs 8.4%, p=0.03) due an excess of cardiovascular death (0% vs 8.4%, p=0.008), and a higher rate of major bleeding (0% vs 5.3%, p=0.05). However, they showed a similar rates of thromboembolic events (1.3% vs 1.1%, p=0.68), MACE (9.3% vs 13.7%, p=0.26) and MAE (18.7% versus 26.3%, p=0.16) compared to patients on DAPT. A total of 9 patients (5.3%) died during follow-up; 8 (88.9%) of them were on TT, 4 patients had a bleeding event, and 3 of them had a CHA2DS2VASc=1. In a multivariate analysis, in patients with CHA2DS2VASc &lt; 2, the use of TT showed a trend towards increased mortality (OR 8.4; 95% CI: 0.91 to 77.6, p=0.05), and was a predictor of major bleeding (OR 2.9: 1.04-8.25, p=0.042). Conclusions: In patients with non-valvular AF and CHA2DS2VASc &lt;2 submitted to CS, the addition of OAC to DAPT shows a trends to increases mortality as well as the rate of major bleeding, and does not provide any apparent benefit preventing thromboembolic events.
Abstract 229: Outcome of Mild therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest: A Nationwide Retrospective Analysis
Authors: Eui Jung Lee, Sang Do Shin, Kyoung Jun Song, Young Sun Ro, Won Pyo Hong
Journal: Circulation (2013)

Background: MTH has been known to be effective in patients with shorckable rhythm but controversial whether it improves outcomes in patients with non-shockable rhythms or not. This study aimed to determine whether MTH was associated with improved out-of-hospital cardiac arrest (OHCA) outcomes by ECG rhythms. Methods: We used a nationwide OHCA cohort data from 2008 to 2010. We included OHCA survivors of presumed cardiac etiology with age more than 15 years-old, excluding patients with unknown outcome or alert mental status after prehospital return of spontaneous circulation. MTH group was defined as patients received any method of hypothermia. The primary and secondary outcomes were survival to hospital discharge and good neurological recovery. Multivariable logistic regression analysis was used to compare outcome of MTH and non-MTH group in total cohort and propensity-score matched cohort including subgroup analysis by ECG type. Results: Among 64,155 OHCA patients, 4,557 with survived to admission were used for analysis (1,599 survived to discharge and 499 discharged with good neurological recovery). Overall, MTH group had better outcome than non-MTH group in survival to discharge (53.6% vs. 33.4%, p&lt;0.001) and good neurological outcome (18.3% vs. 10.3%, p&lt;0.001). In the total cohort, the adjusted ORs of MTH group compared to non-MTH group were 1.81 (95%CI 1.44-2.29) for survival to discharge and 1.37 (95%CI 1.00-1.89) for good neurological outcome. In the propensity score-matched cohort, adjusted ORs of MTH group compared to non-MTH group were 1.83(95%CI 1.33-2.50) for survival to discharge and 1.20 (95%CI 0.76-1.88) for good neurological outcome. In the subgroup analysis, the adjusted ORs of MTH group compared to non-MTH group for survival to discharge were 2.04(95%CI 1.15-3.62) in shockable rhythm and 2.05 (95%CI 1.51-2.79) in non-shockable rhythm. Adjusted ORs of MTH group to non-MTH group for good neurological recovery were 1.86(95% CI 1.07-3.21) in shockable rhythm and 1.13 (95% CI 0.59-2.20) in non-shockable rhythm. Conclusions: MTH was associated with improved survival to discharge but not good neurological. In a subgroup of shockable rhythm, MTH was associated with better neurological outcome and survival to discharge.
Abstract 221: Pharmacokinetics and Brain Bioavailability of Nitrite Therapy After Ventricular Fibrillation Cardiac Arrest in Rats
Authors: Thomas Uray, Phil E Empey, Tomas Drabek, Travis Jackson, Jason P Stezoski, Samuel A Tisherman, Patrick M Kochanek, Cameron Dezfulian
Journal: Circulation (2013)

Introduction: Nitrite (NO 2- ) reduces neurological damage and myocardial dysfunction after cardiac arrest (CA), likely through a nitric oxide (NO) or S-nitrosothiol mechanism. The pharmacokinetics (PK) and blood brain barrier (BBB) penetration and elimination of nitrite therapy after CA are unknown but have important implications for clinical translation. Prior reports support optimal cytoprotection at blood levels of 10-20 μM. We tested the hypothesis that exogenous nitrite rapidly crosses the BBB and is taken up by tissues, increasing levels in cerebrospinal fluid (CSF), brain and heart. Methods: Rats (total n=23) were subjected to 5 min VF CA followed by 1.5 min CPR/defibrillation. Rats received either 1 ml placebo or nitrite (8μM) intravenously between 5-10 min resuscitation time (RT). Shams (n=6) with or without nitrite treatment were also analyzed. Nitrite blood levels were measured at various times up to 60 min. At 16 min RT (n=13), CSF was obtained, animals perfused with nitrite-free saline and brain, and heart removed. Separate placebo-controlled experiments (n=6) measured blood nitrite clearance during the initial hour RT. Tissue nitrite concentrations were calculated based on wet tissue weight. Results: Blood nitrite levels were 57.14±10.82 μM at 11 min RT in the nitrite groups, respectively, vs. 0.94±0.58 μM in placebo (p&lt;0.001). Blood nitrite rapidly declined in the initial 2 min after dosing (distribution) reaching 73% of peak values with a more gradual elimination (beta t ½ = 25 min) subsequently. Nitrite rapidly crossed the BBB and was present in CSF at 17.1±1.1 min RT in levels comparable to plasma. Heart and brain had more modest 2-3 fold increases. Conclusions: Nitrite given after CA rapidly crosses the BBB and the PK data suggest significant tissue uptake. These data provide a biological basis for potential cytoprotection including the brain and will inform clinical trials regarding optimal dosing.
Abstract 15300: Vigorous Physical Activity in the Women’s Health Initiative Cohort: Good or Maybe Not So Good?
Authors: Yvonne L Eaglehouse, Evelyn O Talbott, Yuefang Chang, Lewis H Kuller
Journal: Circulation (2015)

Introduction: Studies primarily of athletes have suggested that high levels of vigorous physical activity (PA) may increase the risk of amyotrophic lateral sclerosis (ALS). Case-control studies provide equivocal support for this hypothesis. Hypothesis: There have been no prior large cohort studies that have evaluated the relationship between vigorous PA, other risk factors, and subsequent ALS mortality among women. Methods: The Women’s Health Initiative (WHI), mean age of 63.6, assessed strenuous or hard PA, defined as PA that resulted in a sweat or fast heartbeat, at baseline by a self-administered questionnaire. Frequency of strenuous activity per week and duration in 20-minute intervals was collected. Metabolic equivalent (MET) intensity scores were then used to calculate the MET equivalence per week, similar to what had been used in previous WHI studies of PA. There were 165 women who were identified with ALS as the cause of death over an average 9.5 years follow-up. We excluded 4 deaths within 2 years of baseline evaluation. Results: Women who died from ALS were older and were predominantly white, n=145 (90%). Total hours of recreational PA was positively related to death due to ALS (p=.03) as was energy expenditure from strenuous activity (p=.045) and minutes of strenuous activity per week. In multivariate Cox models, duration of very hard or strenuous activity &gt;40 minutes per week increased the hazards ratio of ALS, 1.67 (1.10-2.55, p=0.09 for trend), over time. Interestingly, the risk from performing no strenuous PA compared to some is similar in magnitude for total mortality [1.19 (1.12-1.27) based on 21,529 deaths], for CHD incidence [1.23 (1.10-1.37) based on 7,767 CHD events], and for breast cancer incidence [1.13 (1.03-1.25) based on 8,722 breast cancer deaths] in the WHI. Conclusions: This is the first cohort study that reported relationship of vigorous PA to risk of ALS even in sedentary participants. The protective effect of strenuous PA for total mortality, CHD, and breast cancer compared to the very small effect of strenuous PA on ALS risk does not compromise the overall benefit of vigorous exercise, but may provide an important clue as to the etiology of ALS.
Abstract 14952: Disruption of a Newly Identified Complex Between soluble Guanylyl Cyclase and Connexin 43 is Potentially Linked to Cardiac Contractile Dysfunction
Authors: Pierre-Antoine Crassous, Can Huang, Ping Shu, Peter Brouckaert, Lai-Hua Xie, Annie Beuve
Journal: Circulation (2015)

Background: The role of nitric oxide (NO) in regulation of excitation-contraction (EC) coupling remains controversial. NO activates soluble Guanylyl Cyclase (sGC), a heme-containing heterodimer (α/ß subunits), to increase cGMP production and regulate downstream targets such as Protein Kinase G (PKG) and phosphodiesterases (PDE). Intercalated discs (ID) are essential for electro-mechanical coupling between cardiomyocytes. Connexin 43 (Cx43) via formation of gap junctions at the ID mediate the electrical coupling. Cx43 targeting and assembly at the ID involved phosphorylation by many protein kinases, including cAMP-activated PKA. In various cardiomyopathies such as arrhythmia, Cx43 is relocated from ID to the lateral membrane of cardiomyocytes. Recently, we discovered that sGCβ is localized at the ID with Cx43 and PDE3A, using immunofluorescence (IF) and Triton/Urea heart fractionation. Importantly, we showed by co-immunoprecipitation (co-IP) that sGC physically interacts with Cx43 in the heart. Hypothesis: Cx43 assembly and function at the ID through PKA-dependent Cx43 phosphorylation depends on NO-sGC-cGMP microdomain inducing inhibition of PDE3A. Methods and Results: To assess the role and relevance of the sGC-Cx43 complex, we used Angiotensin II (AngII) to induce cardiac hypertrophy and arrhythmia in wild-type (WT) mice and sGCα-KO mice, which are depleted for sGC activity. Co-IP indicates that sGC-Cx43 complex is decreased in AngII-treated WT (n=5), independently of decreased Cx43 expression and IF showed Cx43 lateralization. NO-dependent cGMP in membrane fraction of AngII-hearts was decreased by 50%. Conversely, in sGCα-KO mice Cx43-sGC complex was reduced and even more so with AngII treatment. In addition to a significant increased cardiac hypertrophy in sGCα-KO mice (heart to body weight ratio KO: 5.16±0.19 vs WT: 4.45±0.04, n=4-8, P&lt;0.05), preliminary EKG (n=4) indicates that sGCα-KO mice suffer from cardiac arrhythmia with, intriguingly, alteration in P waves. Conclusion: Altogether, our data suggest that sGC via modulation of Cx43 location at ID is potentially involved in EC regulation. We currently explore the mechanism underlying these observations with in vivo, biochemical approaches and imaging.
Abstract 19227: Impact of Health Literacy on the Length of Delay in Seeking Care After Worsening of Symptoms in Patients With Heart Failure
Authors: Miyuki Tsuchihashi-Makaya, Shiho Matsuoka
Journal: Circulation (2013)

Background: Repeated admissions in patients with heart failure (HF) are related to a delay in responding to HF symptoms. In order to adequately react to HF symptoms, HF knowledge and taking decisions to seek care are essential. Although previous studies have reported that health literacy (HL) was associated with decision making in chronic conditions, little is known on the impact of HL on their behavior for seeking treatment. We analyzed the hypothesis that HL is associated with a delay in seeking care in patients with HF. Methods: This cross-sectional study analyzed the data of 112 hospitalized patients with HF (mean age, 69.6 ± 11 years; 68% males; mean left ventricular ejection fraction 49.6 ± 21%). During index hospitalization, a structured interview was conducted to assess the type of worsening HF symptoms and length of delay in seeking care. Patients completed questionnaires on depressive symptoms and HL (functional, communicative, and critical HL). Clinical and demographic data were also collected. Linear regression analysis was performed to examine whether HL was independently associated with time to seeking care. Results: Median patient delay time was 32 h, with 38 patients reporting short delay (&lt;12 h) and 40 patients reporting long delay (&gt;96 h). Patients having a long delay were more likely to be females and have no history of myocardial infarction or HF. Loss of appetite, fatigue, weight gain, and dyspnea on exertion were related to long delay. Levels of communicative and critical HL were associated with long delay (communicative HL short delay, 12.9 vs. long delay, 8.9, P = 0.024; critical HL short delay, 10.2 vs. long delay, 8.0, P = 0.043). After adjusting for confounding factors, communicative and critical HL were shown to be independent predictors of the length of delay in seeking care (communicative HL β = –0.176, P = 0.031; critical HL β = –0.314, P = 0.033). Conclusions: Communicative and critical HL were factors associated with higher risks for delay in seeking care in patients with HF. In order to reduce the delay time, patients with low HL require enhanced education regarding recognition of HF symptoms and the appropriate actions that need to be taken to avoid worsening of symptoms.
Abstract 225: Healthcare Provider Perspectives on Resuscitation of Drug-Related Out-of-Hospital Cardiac Arrest
Authors: Allison Koller, David D Salcido, Clifton W Callaway, James J Menegazzi
Journal: Circulation (2013)

Introduction: Out-of-hospital cardiac arrest from drug overdose (OD-OHCA) caused over 38,000 deaths in 2010. A preliminary study in Pittsburgh found that OD-OHCA patients differed demographically and in the resuscitation treatments they received, despite identical American Heart Association (AHA) resuscitation guidelines. We hypothesized that physician and non-physician healthcare provider perceptions affect decision-making in the treatment of OD-OHCA versus non-OD OHCA. Methods: A handwritten survey was administered at the National Association of EMS Physicians 2013 Scientific Assembly between January 9 and 12, 2013. Participants were asked about their affiliated EMS agencies, perceptions of OD-OHCA incidence and abused drugs, and perspectives on and knowledge of the treatment of OD-OHCA during resuscitation. Participants were instructed to complete only one survey. Results: In sum, 193 respondents participated in this survey: 144 (75%) were physicians and 49 (25%) were non-physician healthcare providers. Of the physicians, 79% identified current status as a medical director and 76% of non-physicians identified as a paramedic. Eighty-three percent of physicians and 65% of non-physicians indicated that OD-OHCA patients had different demographics than non-OD OHCA; 64% all respondents felt that OD-OHCA patients should be treated differently. Of those respondents who believed that OD-OHCA patients should be treated differently, 47% believed there were differences in the AHA guidelines, while only 27% of those respondents who believed that OD-OHCA patients should not be treated differently believed that AHA guidelines recommended differential treatment. Fifty-four percent of all respondents reported that they or their paramedics make different decisions when treating OD-OHCA patients, regardless of protocol. Seventy-eight percent of respondents indicated the use of naloxone during OD-OHCA resuscitation while 12% reported administering naloxone during non-OD OHCA resuscitations. Conclusions: Physicians and non-physicians report perceiving OD-OHCA patients differently than non-OD and making different treatment decisions based on these perceptions. This may result in etiology-oriented resuscitation for OD-OHCA.
Abstract 19154: Maladaptive Autophagy and Necrotic Death of Ventricular Myocytes Induced by p53 is Contingent Upon Mitochondrial Death Gene Bnip3
Authors: Lorrie A. Kirshenbaum, Yan Wang, Hongying Gang, Rimpy Dhingra
Journal: Circulation (2013)

Myocardial ischemia and angiotensin II activate the tumor suppressor p53 protein, which promotes cell death. Previously, we showed that the Bcl-2 death gene Bnip3 is highly induced during ischemia, where it triggers mitochondrial perturbations resulting in autophagy and cell death. However, whether p53 regulates Bnip3 and autophagy is unknown. Herein, we provide new compelling evidence for a novel signaling axis that commonly links p53 and Bnip3 for autophagy and cell death. p53 overexpression increased endogenous Bnip3 mRNA and protein levels resulting in mitochondrial defects leading to loss of mitochondrial ΔΨm. This was accompanied by an increase in autophagic flux and cell death. Notably, genetic loss of function studies, such as Atg7 knock-down or pharmacological inhibition of autophagy with 3-methyl adenine, suppressed cell death induced by p53-indicating that p53 induces maladaptive autophagy. Our previous work demonstrated that Bnip3 induces mitochondrial defects and autophagic cell death. Conversely, loss of function of Bnip3 in cardiac myocytes or Bnip3-/- mouse embryonic fibroblasts prevented mitochondrial targeting of p53, autophagy, and cell death. To our knowledge, these data provide the first evidence for the dual regulation of autophagy and cell death of cardiac myocytes by p53 that is mutually dependent on and obligatorily linked to Bnip3 gene activation. Hence, our findings may explain more fundamentally, how, autophagy and cell death are dually regulated during cardiac stress conditions where p53 is activated.
Abstract 214: Therapeutic Hypothermia Promotes Arrhythmogenic Calcium-Mediated Delayed Afterdepolarizations During Sympathetic Stimulation
Authors: Hidehira Fukaya, Shalen Kouk, Bradley N Plummer, Aurelia Cheng, Joseph S Piktel, Kenneth R Laurita, Lance D Wilson
Journal: Circulation (2013)

Introduction: Most patients who undergo therapeutic hypothermia (TH) suffer cardiac arrest due to ischemia-induced ventricular fibrillation (VF). Ischemia and hypothermia both cause cellular calcium (Ca) overload, a substrate for Ca-mediated triggered arrhythmias. Previously, we showed that under non-ischemic conditions, TH suppresses Ca-mediated arrhythmias. However, the mechanistic relationship between hypothermia-induced Ca dysregulation and arrhythmias during ischemia, the most common clinical scenario, is unknown. We hypothesized that TH and ischemia would synergistically promote spontaneous Ca release and subsequent arrhythmogenic delayed afterdepolarizations (DADs). We examined this relationship during sympathetic stimulation, as occurs when epinephrine is given during resuscitation from VF. Methods and Results: Dual optical mapping of Ca transients and action potentials was performed in canine left ventricular wedge preparations during 10 minutes of no flow ischemia during normothermia (NT, 36°C, n=5) and TH (32°C, n=7) with and without beta-sympathetic stimulation (isoproterenol, 0.2uM, each n=5). Multicellular spontaneous Ca release events (mSCRs) and resultant DADs were induced by rapid pacing. During ischemia, TH increased mSCR amplitude (44±3%) vs. NT (26±4%, p&lt;0.04). In contrast, the slope (amplitude/rise time) of mSCRs, an important determinant of triggered activity (TA), and DAD amplitudes were similar in TH and NT (24±6 and 21%±2% respectively, both p=NS). Importantly, when sympathetic stimulation was present during ischemia, TH increased the amplitude mSCRs compared to NT (61±5 vs. 31±7%, respectively p&lt;.01) and the slope of mSCRs was 2-fold greater (p&lt;.01), resulting in greater amplitude of DADs (50±9 vs. 28±7%, p=.08) and TA was observed. Conclusions: During ischemia, TH is not arrhythmogenic unless sympathetic stimulation is introduced, where it promotes spontaneous Ca release and DADs. Moreover, these data suggest that when TH is initiated during ischemia, as in intra-arrest cooling, sympathetic stimulation during cardiac arrest may be proarrhythmic by increasing susceptibility to Ca-mediated triggered arrhythmias.