tbuckley/cabot-search huggingface dataset:
Abstract 19162: Metabolites Reporting on Mitochondrial Function Predict Response to Biventricular Pacing
Authors: Svati H Shah, Happy Thakkar, Asad A Shah, Nicholas D Andersen, James Bain, Carol Haynes, Michael Muehlbauer, Robert Stevens, Kent Nilsson, Jonathan P Piccini, Jason Koontz, Albert Sun, Christopher B Newgard, Patrick M Hranitzky
Journal: Circulation (2012)

Background. Biventricular pacing has been shown to improve morbidity and mortality in patients with impaired systolic left ventricular function and congestive heart failure who have evidence of dyssynchronous ventricular contraction. However, a significant percentage of patients implanted with a biventricular pacer will not have a beneficial response. Novel molecular technologies may help identify biomarkers to better predict who will benefit most from this therapy. Methods. Individuals undergoing biventricular pacemaker implantation were selected from the ElectroPhysiology GENetics (EPGEN) biorepository (N=120). Targeted, quantitative mass-spectrometry based metabolomic profiling of 63 metabolites was performed on baseline, frozen, fasting plasma samples collected at the time of the index procedure. Positive response to pacing was defined as a 5% improvement in left ventricular ejection fraction or a ≥1 class improvement in New York Heart Association functional class at six months after device implantation. Principal components analysis (PCA) was used to reduce the large number of individual metabolites into a smaller set of uncorrelated factors. Logistic regression was used to test the association between PCA-derived factors and response. Results. A positive response to biventricular pacing was observed in 55 individuals at 6 months (N=65 showing no positive response). PCA identified 13 metabolite factors clustering in biologically plausible pathways. Of these, factor 1 (composed of medium and long chain acylcarnitines, medium and long chain dicarboxylacylcarnitines, ketones and β-hydroxybutyrate) was associated with positive response to pacing (p=0.007). Analyses of the individual metabolites composing this factor showed similar results (p=0.03-0.003). Conclusions. We have identified a cluster of metabolites, many of which are derived from mitochondrial metabolism, that predict a positive response to biventricular pacing. These novel biomarkers may assist in better risk stratification and patient selection for this therapy.
Abstract 19557: Comparative In-Hospital Outcomes for Pericardiocentesis versus Surgical Pericardiotomy in United States
Authors: Riyaz Bashir, Paul L Hermany, Chad J Zack, James B McClurken, Alfred Bove
Journal: Circulation (2012)

Background: The national and comparative in-hospital outcomes and resource utilization for pericardiocentesis and surgical pericardiotomy are not known. Methods: The Nationwide Inpatient Sample (NIS) database was used to identify patients who underwent pericardiocentesis or pericardiotomy from 2005 to 2009 in the United States. We used propensity score matching and the Elixhauser index for comorbidity adjustment to compare in-hospital outcomes and resource utilization among matched groups of patients that underwent either pericardiocentesis or pericardiotomy. Results: Among a total of 131,945 patients who underwent either procedure during the study period, 17,565 patients were divided into two matched groups of pericardiocentesis (9,336 patients) and pericardiotomy (8,229 patients). The pericardiocentesis group had significantly higher in-hospital mortality than the pericardiotomy group (15.7% vs. 10.4%, p&lt;0.001). Patients in the pericardiotomy group had a significantly higher rate of blood transfusions (22.6% vs. 19.5%, p&lt;0.001), post-procedural respiratory complications (2.0% vs. 0.8%, p&lt;0.001), iatrogenic pneumothorax (8.1% vs. 3.1%, p&lt;0.001), post-operative hemorrhage (3.1% vs. 1.8%, p&lt;0.001), and post-operative hematoma (1.5% vs. 1.0%, p=0.001). The average length of stay was longer in the pericardiotomy group than in the pericardiocentesis group (12.6 vs. 8.5 days, p &lt;0.001). The average hospital charges were also higher in the pericardiotomy group than in the pericardiocentesis group ($108,624 vs. $75,690, p&lt;0.001). Conclusion: In this observational study, we found that pericardiocentesis is associated with a significantly higher in-hospital mortality than surgical pericardiotomy while the latter is associated with higher rates of post-operative morbidity and resource utilization.
Abstract 19085: Cross-bridge Activation at Diastolic Calcium Levels in Human Myocardium
Authors: Brad Palmer, Cameron Donaldson, Markus Meyer, Peter VanBuren, Michael Zile, Martin LeWinter
Journal: Circulation (2012)

Tropomyosin is positioned on actin in dynamic equilibrium as a function of free calcium concentration. However, it is estimated that ∼5% of the myosin binding sites on actin are exposed at low calcium levels (e.g. pCa 8) raising the possibility of myosin cross-bridge formation at diastolic calcium levels. We tested this hypothesis in detergent-treated (skinned) strips dissected from epicardial biopsies obtained from male patients during coronary bypass grafting. Patients (n=15) had normal left ventricular (LV) ejection fraction and wall motion. Eight control (C) patients had neither hypertension (HTN) nor diabetes mellitus. Seven patients had HTN and concentric remodeling with increased LV wall thickness/radius ratio. Western blot analysis of skinning supernatant revealed no loss of tropomyosin or troponin-I that would implicate loss of normal thin filament regulation during the skinning process. Myofilament calcium sensitivity at sarcomere length 2.2 μm was similar between C and HTN (pCa 50 6.07±0.07 vs 6.06±0.04). Tension at pCa 8 was similar between C and HTN (4.26±0.52 vs 4.30±0.51 mN.mm -2 ), but was significantly reduced by application the cross-bridge inhibitor 2,3-butanedione monoximine (BDM) (2.15±0.24 vs 3.01±0.40 mN.mm -2 , p&lt;0.05). The higher tension in HTN with BDM reflects a greater inherent stiffness in HTN independent of cross-bridges. We then used sinusoidal length perturbations (0.125-250 Hz) to detect the detachment rate of cycling cross-bridges. In both C and HTN strips, frequency-dependent viscoelastic characteristics of cycling cross-bridges were apparent at pCa 8 and abolished with BDM. At pCa 8 cross-bridge detachment rate was significantly greater in C than HTN (106.1±12.5 vs 74.6±9.3 s -1 , p&lt;0.05). These results indicate that there are cycling cross-bridges in normal and concentrically remodeled human myocardium at diastolic calcium levels that contribute to diastolic tension. Furthermore, the rate of cross-bridge detachment under relaxed conditions is slower in concentrically remodeled myocardium from HTN compared with C patients. The presence and lifetime of cross-bridges formed in addition to cross-bridge independent stiffness must be considered as significant contributors to diastolic dysfunction in HTN.
Abstract 19124: Detection and Prevalence of Systemic Atherosclerosis: Results from the High-Risk Plaque (HRP) Initiative
Authors: Usman Baber, Samantha Sartori, Roxana Mehran, Pieter Muntendam, Mario J Garcia, Henrik Sillesen, Erling Falk, Valentin Fuster
Journal: Circulation (2012)

Background Most studies examining the burden of atherosclerosis involve a single anatomic territory. Such approaches, however, underestimate the true prevalence of vascular disease as atherosclerosis is a systemic, rather than focal, process. We sought to determine the prevalence and clinical correlates of systemic polyvascular atherosclerosis in an asymptomatic US population. Methods In the High-Risk Plaque (HRP) Initiative, 5823 asymptomatic adults underwent multimodality non-invasive imaging for evaluation of subclinical atherosclerosis in the carotid and coronary arteries using duplex ultrasound and computed tomography (CT). Subclinical atherosclerosis was defined as presence of any coronary calcification (score &gt; 0) or any focal carotid plaque. Patients were categorized by number of vascular territories with atherosclerosis (0, 1 or 2) and by quartiles of carotid atherosclerotic burden. Results Any subclinical atherosclerosis was common, detectable in 87.8% (n=5113) of participants. While 1772 (30.4%) of individuals had involvement of either the coronary or carotid arteries alone, 3341 (57.4%) had involvement of both territories. Significant clinical correlates of polyvascular atherosclerosis included male gender, older age, diabetes mellitus, white race, smoking status and systolic blood pressure (p &lt;0.001). The positive predictive value (PPV) for detecting any carotid plaque with an abnormal calcium score was 85% while the PPV for any coronary calcium with carotid plaque was 74%. In addition, the prevalence of coronary calcification increased in a step-wise fashion with greater carotid atherosclerotic burden (Figure). Conclusion In the HRP Initiative, traditional risk factors correlated strongly with greater prevalence of subclinical atherosclerosis. Testing in one territory is strongly associated with probability of disease in the remaining vascular bed, highlighting the systemic nature of atherosclerosis.
Abstract 81: Feasibility of Using Hospital Personnel to Create a Sustainable CPR Training Program for Family Members of Hospitalized Patients
Authors: Audrey L Blewer, Jeffrey Le, David Buckler, Marion Leary, Barbara Riegel, Bentley J Bobrow, Benjamin S Abella
Journal: Circulation (2012)

Background: Bystander CPR rates for cardiac arrest are low in many communities. This is especially the case in the home environment, where fewer potential rescuers are present than in public areas, and CPR training may be lacking. While recent studies have evaluated using the hospital as a unique “point of capture” for family member CPR training using paid research staff, there is a crucial need to develop a low cost, sustainable, CPR education program for patient families. Objectives: We sought to evaluate the feasibility of using hospital personnel (nurses and volunteers) to implement our CPR Anytime Hospital-Initiated Training Program (CHIP) using an established video self-instruction (VSI) kit for family members of hospitalized adult patients with coronary disease or significant cardiovascular risk factors. Methods: In an ongoing multicenter trial of CPR educational strategies, hospital personnel were sought to implement the CHIP program. After training, hospital personnel and family member impressions on training were assessed using mixed quantitative and qualitative survey instruments. Survey responses were analyzed for statistical significance. Results: From 02/2012 to 05/2012, hospital personnel from 4 institutions trained 120 family members in CPR; 86/120 (72%) of the family members were never CPR trained or had not received training in over 10 years. When queried about the program, 119/120 (99%) of the trainees indicated that they felt comfortable learning CPR skills in the hospital environment, and 97/120 (81%) of trainees felt confident using their new skills in a real-life situation. Of 21 hospital personnel (11 nurses, 10 volunteers), 94% felt confident conducting the program. Nurses more frequently indicated that the family members were receptive to participating in the program (Likert scale (1-5) mean score 4.22 + 0.83, 3.77 + 1.39, p=ns). Overall, 94% of the personnel felt that the service was beneficial to families and patients. Conclusions: The hospital setting offers a unique “point of capture” to provide CPR instruction to an important, undertrained population. This work suggests that implementation of VSI training programs using hospital personnel is feasible and may confer broader dissemination of life-saving skills.
Abstract 299: The Cardioprotective Mechanism of a Recombinant Atrial Natriuretic Peptide Against Catecholamine-Induced Myocardial Injury in Acute Heart Failure
Authors: Wakako Murakami, Shigeki Kobayashi, Akihiro Hino, Masakazu Fukuda, Takayoshi Kato, Shinichi Okuda, Masahiro Doi, Takeshi Yamamoto, Masafumi Yano, Masunori Matsuzaki
Journal: Circulation (2012)

Background: Catecholamine induces intracellular reactive oxygen species (ROS), enhances abnormal Ca 2+ handling and leads to apoptosis in failing cardiomyocytes. We clarified the mechanism by which an exogenous atrial natriuretic peptide (ANP) exerts cardioprotective effect in patients with acute heart failure (HF). Methods and Results: Blood sampling from both coronary sinus and aorta showed that cardiac tissue produced 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in patients with HF(n=30), but not in control subjects (n=10). Urinary (U) 8-OHdG (ng/mg creatinine) also increased in only patients with HF(Control;8.0±2.0 vs HF; 14.8±2.5, p&lt;0.05). As protocol 1, we examined whether an infusion of ANP (0.025 µg/kg/min) decreased levels of U-8-OHdG during the treatment of HF (n=15, for 3 days), as compared with that of nitroglycerin (NTG) (n=15, for 3 days). Either treatment with ANP or NTG similarly improved hemodynamic parameters and BNP. In ANP-treated group, however, U 8-OHdG significantly decreased as compared with in NTG-treated group (ANP: 9.8±3.5; NTG: 14.5±4.2, p&lt;0.05). As Protocol 2, we investigated the effect of ANP on 1) intracellular ROS production by DCFH-DA, 2) local Ca 2+ release event by confocal microscopy using Fluo 4-AM, 3) myocyte apoptosis (TUNNEL staining) and survival rate after 48h in failing myocytes isolated from LV in canine tachycardia-induced HF(n=6, EF 20 ± 5%). In failing myocytes, isoproterenol (ISO) markedly increased intracellular ROS, concurrently with an increase in the frequency of Ca2+ sparks (SpF:s -1 •100µm -1 :HF: 8.0 ± 2.0 , Normal: 1.6 ± 0.5, p&lt;0.01) . Interestingly, in failing myocytes, ANP(1x10 -8 mol/L) significantly suppressed the ISO-induced ROS production, SpF, and myocyte apoptosis respectively. Eventually, the survival rate (%)in failing myocytes was significantly lower in the presence of ISO than in its absence, while it was significantly improved by co-incubation of ISO plus ANP (ISO(-);59±12, ANP(+); 63±8, ISO(+);33±13, ISO plus ANP; 55±5, p&lt;0.01). Conclusions: ANP has a potent antioxidant action against catecholamine-induced ROS, which may correct abnormal Ca 2+ release and inhibit myocyte apoptosis, eventually contribute to improvement of myocytes survival in HF.
Abstract 8910: <i>In Vitro</i> and i <i>n vivo</i> Performance of a Completely Autologous Aortic Valved Conduit (BIOVALVE Type VII) Prepared by in Body Tissue Architecture Technology Using a Novel Separable Mold
Authors: Yasuhide Nakayama, Yoshiaki Takewa, Hirohito Sumikura, Yuichi Matsui, Masashi Yamanami, Yuichiro Kishimoto, Mamoru Arakawa, Kentaro Omuma, Takeshi Mizuno, Tomonori Oie, Keiichi Kanda, Eisuke Tatsumi
Journal: Circulation (2012)

Purpose: In body tissue architecture technology, attempted as novel and practical regeneration medicine by us, can prepare a completely autologous valved conduit (BIOVALVE) consisting of only recipient’s own tissue. In this study, the latest type of BIOVALVE was successfully implanted as an aortic valve in a goat model after in vitro evaluation with a pulsatile circulation circuit. Methods and Results: BIOVALVEs with 3 leaflets in the inner side of the conduit with the sinus of Valsalva were prepared by 2-month embedding of the specially designed separable molds, assembled using 5 plastic parts, in the dorsal subcutaneous spaces of goats. The valve tissue formation in the body was observed non-invasively by wireless capsule endoscope, impregnated into the molds. The obtained BIOVALVE had adequate mechanical properties including highly pressure resistance close to native valves. In vitro evaluation using a pulsatile circulation circuit (LaboHeart NCVC, IWAKI) showed that good valvular function (regurgitation: less than 15%) at mean flow rate of 4.8 L/min, AoP of 129-49 (82.2) mmHg, and beating rate of 70 and high durability (over 1 month). BIOVALVEs (n=3) were implanted in the specially designed apico-aortic bypass of goats to evaluate the possibility as an aortic valve for 1 month. Postoperative echocardiography showed smooth movement of the leaflets with little regurgitation under systemic circulation (2.6 ±1.1 L/min). The luminal surface after implantation was very smooth and covered with thin pseudointima without thrombus formation. Conclusion: Completely autologous BIOVALVE type VII developed satisfied the higher requirements of systemic circulation in vitro and in vivo and has potentiality for clinical application.
Abstract 19419: Algorithm-Based Vendor Selection for Implantable Cardiac Devices Reduces Costs and Avoids Appearance of Conflict of Interest
Authors: Charles A Henrikson, Eric C Stecker, Karl Stajduhar, Thomas Clark, Jack Kron
Journal: Circulation (2012)

Introduction: In most hospitals, device vendor selection for an individual case is at the discretion of the implanting physician. This exposes the physician to the appearance of conflict of interest and may increase device costs. Methods: At a single academic center, implanting physicians and electrophysiology lab staff constructed and implemented a device selection algorithm based on referring provider request, device features, and equal distribution of cases among the four vendors in our geographic area. Costs for comparable devices were also incorporated into the algorithm, and lower cost devices were selected if all other factors were equal. For each individual case, the algorithm was followed by technical and administrative staff who selected and notified the vendor. Information was solicited from the implanting physicians to inform algorithmic selection. The selection algorithm could be overruled at discretion of implanting physician on clinical grounds. When manufacturer-specific features were selected or non-algorithmic clinical factors incorporated into the decision, the rationale was documented. Results: Over a three-year period of implementation, this algorithm resulted in a distribution of cases among vendors (15.4% Biotronik, 19.0% Boston Scientific, 35.4% Medtronic, and 30.0% St Jude Medical). Imbalances were due to referring provider preferences and the incorporation of cost considerations into the algorithm. In no instance did the implanting physician overrule the algorithm. There were no complaints from referring providers. As compared to prior to the implementation of the algorithm, approximately $750,000 was saved over three years, an 8.3% reduction in device costs. This was largely on the basis of algorithmic selection of less expensive (older generation) devices for appropriate patients. After two years, when vendor contracts were renegotiated, substantial further cost savings were realized. Conclusions: A device selection algorithm removes the daily task of vendor selection from the physician and removes the appearance of conflict of interest. The algorithm also results in a substantial cost savings for the hospital. We hope this model will find broad application in the electrophysiology community.
Abstract 8129: A Novel Mutation in HERG Leading to an LQTS Overlap Syndrome
Authors: Ravi Shah, Jodi Zilinski, Farhad Abtahian, Saumya Das
Journal: Circulation (2011)

Background: Although mutations and corresponding clinical characteristics of subclasses of long QT syndrome (LQTS) have been described, patients may exhibit “overlap syndromes” not corresponding neatly into classic LQTS phenotypes. Here, we report a novel mutation in the HERG potassium channel associated with LQTS. Case presentation: A 36-year-old female with a recurrent syncope presented with loss of consciousness. There was no family or personal history of sudden cardiac death or other cardiovascular disease. Her examination was normal, except for marked sinus bradycardia (49/min). Her initial electrocardiogram (Figure A) disclosed a prolonged QTc interval (620 ms). Transthoracic echocardiography was normal. While sleeping, she had an episode of polymorphic VT (Figure B), and after temporizing with isoproterenol, she underwent implantation of a dual-chamber pacemaker-ICD, programmed for atrial pacing at 80/min. On review of her ECG, she had a broad-based T wave without notching, consistent with an LQT1 phenotype. However, her presentation of bradycardia, nocturnal episodes, and QT interval shortening with tachycardia (rate-adaptive QT shortening) suggested LQT3. We discovered a novel nonsense mutation (G208T) in the potassium channel KCNH2 (HERG), the cause of LQT2, leading to a premature stop codon near the N-terminus of KCNH2, with a non-functional gene product and reduced functional potassium channel expression. Pacing with beta-blockade normalized her QT interval by 6 months (Figure C), suggesting compensation for an altered IKr current by the IKs current (responsive to sympathetic stimulation). She has remained arrhythmia-free at 6 months. Conclusion: We report the identification of a novel mutation in HERG leading to a LQTS syndrome. Although gene-specific clinical phenotypes are well defined in LQTS, our case identifies an unusual case of an LQTS “overlap syndrome,” with non-classical clinical, electrocardiographic, and genetic data.
Abstract 19822: Ldlr Splice-Site Mutation (ivs9-1g&gt;A) Identified by Whole-Exome Sequencing in an Extended Family with Myocardial Infarction
Authors: Ingrid Brænne, Anja Medack, Klaus Stark, Sarah Field, Salih Tuna, Panos Deloukas, Nilesh J Samani, Heribert Schunkert, Christian Hengstenberg, Jeanette Erdmann
Journal: Circulation (2012)

Introduction: Large genome-wide association studies have identified a number of chromosomal loci for CAD and MI, which display clear significance yet weak absolute effects for disease manifestation. Combined, these loci explain only a small fraction of the expected heritability. Aim: Here we analyzed a rare extended family with clustering of MI/CAD by means of whole-exome-sequencing (WES) to reveal rare disease-causing variants, which may provide new insights in the cause of the disease. Methods: Primarily, we analyzed three affected cousins of a German MI family with 13 affected and 56 unaffected family members by WES using the Agilent SureSelect 38 Mb Kit. Variants were validated by Sanger re-sequencing. Results and Discussion: We identified 19,870 variants shared by all three sequenced family members. Of these, 17,268 variants were found in dbSNP with a frequency &gt;1%. Of the remaining 2,602 variants, 935 are conserved (46 Way) and again 728 are located outside of regions of segmental duplication. To identify function-altering variants we filtered all variants based on avsift score &gt;0.05 and ,,HIGH“ effect predicted by Annovar and SNPEFF, respectively. Due to the relative large number of potentially disease causing variants, we focused on the variants not known in dbSNP. This approach left three variants. One variant, a single base-pair substitution (G&gt;A) in intron 9 of the LDLR gene, was validated by Sanger re-sequencing. This variant lies in the acceptor splice-site of exon 10 (c.855-1G&gt;A) and leads the loss of exon 10 (loss of 76 AA) in the LDLR domain class B repeat. We sequenced all family members available for genetic analysis and found that the variant co-segregates with MI. Mutation carriers had -on average- elevated LDL cholesterol (LDLC) levels (211 vs 141mg/dL), but with variable plasma levels (116-274mg/dL), such that severe hypercholesterolaemia was not observed in our index patient. Conclusion: Using WES we identified the disease-causing variant for this familial form of MI in the LDLR . Interestingly, highly varying LDLC levels initially impeded the diagnosis of heterozygous familial hypercholesterolaemia. This work clearly show the power of systematic WES approaches for identification of disease causing variants within families.
Abstract 17512: Toll-Like Receptor 4 Dependent Macrophage Activation is Critical in Spinal Cord Ischemia-Reperfusion Injury
Authors: Marshall T Bell, Ferenc Puskas, Viktor A Agoston, Joseph C Cleveland, David A Fullerton, Fabia Gamboni, Paco Herson, Xianzhong Meng, Phillip D Smith, Michael J Weyant, Brett ReeceT
Journal: Circulation (2012)

Marshall T Bell 2012 Finalist and Presenting Author