tbuckley/cabot-search huggingface dataset:
Abstract 18926: Pre-Implant Surface EKG Screening Predicts the Arrhythmia Detection Vector Utilized by an Entirely Subcutaneous Implantable Defibrillator System
Authors: Joshua D Moss, Lizbeth Mino, Bradley Knight, John F Beshai, Hemal M Nayak, Martin C Burke
Journal: Circulation (2013)

Objectives: The subcutaneous ICD system (S-ICD) uses 3 electrodes under the skin to detect ventricular arrhythmias. Pre-implant surface EKG is performed to screen for sensing suitability prior to implant. We studied whether screening vectors pre-implant predict the final S-ICD detection vector selected post-implant. Methods: Pre- and post-implant sensing data from 51 patients who received the S-ICD at 2 centers were analyzed. The surface EKG data was collected using a Zoom™ programmer (Boston Scientific) in a configuration simulating the S-ICD sensing vectors (Figure). Surface EKG vectors deemed acceptable at screening were compared to the device-selected arrhythmia detection vector both at implant and during postural testing at hospital discharge. Results: On average, 1.8 +/- 0.6 pre-implant surface screening vectors were deemed acceptable. The detection vector selected 1) at implant and 2) at discharge matched an acceptable pre-implant vector in 80% and 78% of patients, respectively. The vector selected at discharge matched the implant vector in 56% of patients with 1 acceptable screening vector, versus 86% of patients with &gt;1 acceptable screening vector (P=0.03). Vector at discharge was more likely to match a screening vector when the surface proxy for the “primary” sensing vector was deemed acceptable, as compared with the “alternate” sensing vector (P=0.01). Conclusions: The majority of patients had more than one acceptable sensing vector via pre-implant screening EKG. Acceptable sensing vectors determined pre-implant predict the detection vector ultimately selected after implant. In the majority of patients, postural changes at pre-discharge testing do not alter the optimal detection vector.
Abstract 18933: Cardiac Magnetic Resonance 4D Flow: An in vitro Validation of Bioprosthetic Mitral Valve Flow Volume Quantification
Authors: Mohamad G Ghosn, Matthew S Jackson, Dimitrios Maragiannis, Karen Chin, Stephen R Igo, Dipan J Shah, Stephen H Little
Journal: Circulation (2013)

Background: Phase contrast cardiac magnetic resonance imaging allows for the simultaneous acquisition of morphology in 3D (x, y, and z directions) and time-resolved blood flow velocities (known as 4D flow MRI). The clinical applications of this methodology continue to be developed. For this study, we sought to evaluate the methodology and accuracy of 4D flow MRI for the quantification of diastolic flow volume across bioprosthetic mitral valves (BMV) in a controlled and reproducible in vitro system. Methods: BMV of 3 sizes (27, 29, and 31 mm) were consecutively mounted in an MRI compatible flow loop. Flow conditions within the flow loop were set using control software that programmed a pump to generate pulsatile, physiologic ventricular ejection and filling characteristics. Diastolic flow volumes of ~70, 90, and 110 ml/beat were tested for each valve at a beat rate of 70 bpm. An in-series ultrasonic flow transducer (UFT) was used to measure flow (L/min) by which diastolic flow volumes were determined. The acquisition of 3D cine (4D flow) phase contrast velocity data was acquired in a 1.5 Tesla MRI scanner (Siemens) and flow measurements were determined “offline” at 3 locations within the valve; valve base, leaflet tips, and midway between the base and the tips. Results: When 4D flow volume measurements were compared to UFT diastolic flow volumes, the average difference was -0.2 ± 3.0 ml/beat. For all flow condition tested (n=8), the 4D flow measurements were strongly correlated to the reference standard flow meter, regardless of measurement location within the bioprosthesis (Pearson correlation, r=0.98, 0.99, and 0.99 for the base, mid, and tips location, respectively. P&lt;0.001). Conclusion: 4D flow MRI can be used to directly assess bioprosthetic mitral valve diastolic inflow volume, with considerable accuracy compared to reference standard measure. The imaging plane chosen for trans-valvular flow analysis did not affect the accuracy of the 4D flow measurements.
Abstract 18931: The Effect of Breaking Advanced Glycation End-Products, With or Without Exercise Training on the Cardiovascular Effects of Aging
Authors: Erin Howden, Madelijn Sander-Oudegeest, Graeme Carrick-Ranson, Tom Sarma, Naoki Fujimoto, Shige Shibata, Dean Palmer, Kara Boyd, Arie van Dijk, Maria Hopman, Benjamin Levine
Journal: Circulation (2013)

Introduction: Sedentary aging impairs cardiovascular (CV) structure and function. Lifelong exercise training maintains youthful left ventricular (LV) and vascular structure but has little effect on relaxation. Moreover, exercise has no effect on CV structure when begun later in life, perhaps because of the accumulation of advanced glvcation end-products (AGE). Alagebrium is a crosslink breaker that improves LV compliance in older animals, especially when combined with exercise training. We hypothesised that exercise combined with Alagebrium would improve LV function in sedentary humans. Methods: This was a dual-centre double-blind placebo controlled randomized trial with a 1-year intervention. We recruited 110 healthy subjects from the Dallas, TX (n=62) and Nijmegen, Netherlands (n=48). Subjects were randomized to either: a) no exercise+placebo; b) no exercise+Alagebrium [200mg/day]; c) Exercise+placebo; and d) Exercise+Alagebrium. We measured (VO 2 max) and used 2-D echo for measurement of speckle tracking imaging (global longitudinal strain [GLS], systolic strain rate [SR], early diastolic strain rate [SR] and late diastolic strain rate [AR]). Results: Ninety-nine subjects (age 68±5yrs; 53f/46m) completed the 1-year intervention. There were no group differences at baseline for VO 2 max, GLS, SR, ER or AR. Exercise training increased VO 2 max ( P &lt;0.001) without an additive effect of drug ( P =0.79). There was no effect of drug, training, or any combination on GLS ( P values ranged from 0.24-0.57), SR ( P =0.77- 0.91), ER ( P =0.37- 0.63), AR ( P =0.09 - 0.20) [Table 1]. Conclusion: One-year of exercise training, AGE cross link inhibition or their combination does not significantly improve LV function measured by speckle tracking in previously sedentary seniors.
Abstract 18949: The Relationship of Central Obesity to Clinical Outcome After Percutaneous Coronary Intervention With Drug-Eluting Stent
Authors: Se Jun Park, Hong Seok Lim, Hyoung Mo Yang, Byoung Joo Choi, So Yeon Choi, Gyo Seung Hwang, Joon Han Shin, Seung Jea Tahk
Journal: Circulation (2013)

Objectives: Central obesity in patients with coronary artery disease is directly related with adverse cardiovascular events. The aims of this study were to examine the association of truncal fat accumulation with outcomes after percutaneous coronary intervention (PCI). Methods: In 782 patients (mean age: 60 ± 11 years, 494 male, 63.2%) who underwent PCI for 840 coronary lesions with DES between January 2005 and June 2008, dual-energy X-ray absorptiometry (DXA) was performed to assess total body fat and regional body fat distribution. The primary outcome was defined as a composite of major adverse cardiac events (MACE) including cardiac death, myocardial infarction, and ischemia-driven target vessel revascularization (TVR). Results: During a median follow-up of 54 months, 82 cases of MACE (12 cardiac death, 2 myocardial infarction and 72 TVR) occurred. Percentage truncal fat mass to both legs fat mass ratio (%FMtrunk/FMleg) (2.5 vs 2.2, p=0.001) were higher in MACE group than no MACE group. To determine independent risk factors for MACE, we performed multiple logistic regression analysis and revealed that %FMtrunk/FMleg was an adjusted risk factor for adverse cardiac events after PCI (p=0.011), but not BMI, total fat mass. Conclusion: Poor outcome after PCI with DES is more associated with %FMtrunk/FMleg representing central body fat distribution than other obesity parameters, such as BMI. Therefore patients who had coronary angioplasty with DES might need to have therapeutic intervention for secondary prevention.
Abstract 18923: S-Nitroso Human Serum Albumin versus Inhaled Nitric Oxide for the Treatment of Pulmonary Hypertension in a Chronic Right Ventricle Volume Overload Model
Authors: Alessio Rungatscher, Seth Hallström, Daniele Linardi, Elisabetta Milani, Maddalena Tessari, Giovanni Battista Luciani, Alessandro Mazzucco, Giuseppe Faggian
Journal: Circulation (2013)

Background: The study aimed to compare the acute overall hemodynamic and oxidative stress effects of intravenous S-NO-human serum albumin (S-NO-HSA) infusion and inhaled nitric oxide (iNO) in a chronic left-to-right shunt-induced pulmonary arterial hypertension model. Methods and Results: Male Wistar rats underwent surgical creation of aorto-caval fistula (Qp/Qs&gt; 2.0). After 10 weeks they were randomly treated with human serum albumin (HSA) (controls; n. 25), S-NO-HSA (0.5 μmol/kg/h; n. 30) or iNO (20 ppm; n. 35) for 60 minutes. Right ventricular contractility, right ventricular-vascular coupling and ventricular interdependence were assessed in vivo at different preloads by biventricular conductance catheters prior and after 60 minutes treatment. Heart and lung biopsies were obtained to determine oxidative stress by oxidized to reduced glutathione (GSSG/GSH) ratio and high-energy phosphates content. Both S-NO-HSA and iNO led to a significant reduction in right ventricular afterload expressed by effective pulmonary arterial elastance (Ea) (from 1.3 ±0.2 to 0.5 ±0.3 and 0.4 ±0.2 respectively; P&lt; 0.001). Only S-NO-HSA significantly improved right ventricle diastolic function (slope of end-diastolic pressure-volume relation) and contractility indicated by end-systolic elastance (Ees). Therefore a significant increase in the efficiency of ventricular-vascular coupling (Ees/Ea) occurred after S-NO-HSA but not iNO treatment (from 0.33 ±0.15 to 0.98 ±0.21; P&lt; 0.005 and from 0.35 ±0.16 to 0.45 ±0.18; P&lt; 0.1 respectively) with significant increase in left ventricular stroke volume (58 ±7 vs 18 ± 9 %; P&lt; 0.003). S-NO-HSA compared to iNO improved right ventricle phosphocreatine content (27.08 ±11.35 vs. 8.41 ±1.80 nmol/mg protein; P&lt;0.001) and myocardial energy charge (0.85 ±0.03 vs. 0.78 ±0.03; P&lt;0.01). Both S-NO-HSA and iNO decreased lung and right ventricular GSSG/GSH ratio (P&lt;0.001). CONCLUSIONS: S-NO-HSA is more effective than iNO in treating pulmonary hypertension, improving right ventricle diastolic function and right ventricular-arterial coupling with a positive effect on ventricular interdependence. This results in superior energetic reserve of the heart, despite similar reduction of lung and right ventricular oxidative stress.
Abstract 18911: Prognosis of Latent Systolic Dysfunction in Patients Referred for Stress Echocardiography With Normal LV Ejection Fraction
Authors: Azhar A Supariwala, Waddy Gonzales, Matthew Pierce, Jonathan Kahan, Yathin Thammaiah, Swathi Sangli, Manideep Duttuluri, Poonam Pai, Farooq A Chaudhry
Journal: Circulation (2013)

Background: Tissue Doppler imaging can assess latent systolic function. The prognostic impact of latent systolic dysfunction in patients with normal ejection fraction is limited. Methods: We measured the left ventricular septal S wave velocity (Sm) at rest in 908 patients, mean age 58 ±14 years, 40% males who were referred for stress echocardiography with normal left ventricular ejection fraction (&gt;55%). Results: There were 42 (5%) deaths during the mean follow-up of 3.1 ± 0.6 years. Only 44 (6%) had ischemia on stress echocardiogram. There were significant high correlations observed between age and Sm and E′ (r= -0.24; p&lt;0.001 and r= -0.53; p&lt;0.001, respectively) and very high correlations were observed between Sm and E′ (r =0.51; p&lt;0.001). After adjusting for age, gender, CAD risk factors, and ischemia, and interaction of age*Sm, higher age (HR=1.01; 95% CI: 1.004 - 1.01; p&lt;0.001) with normal S wave velocity, and higher S wave velocity (HR = 0.51; 95% CI: 0.36 - 0.73; p&lt;0.001) independent of age were the predictors of mortality. Similarly, diastolic dysfunction was a predictor of mortality (HR= 0.56; 95% CI = 0.41 - 0.76; p&lt;0.001). [FIGURE] However, addition of Sm in the model after E′ or addition of E′ after Sm does not affect the model. On sub-group analyses, taking only patients with diastolic dysfunction same results were observed. Lower Sm and E′ septal both were predictors of worse outcomes but dependent on each other. Conclusion: Latent systolic dysfunction and diastolic dysfunction are highly correlated and associated with worse outcomes in patients with normal ejection fraction. Further studies with large cohort and longer follow-up are needed to determine whether these basic indices can prognosticate this cohort.
Abstract 13935: Predictors for the Improvement of Cardiac Symptoms After Renal Stenting; Multicenter Retrospective (PREMIERE) Registry Study
Authors: Yuri Narishige, Osami Kawarada, Shingo Sakamoto, Koichiro Harada, Teruo Noguchi, Hisao Ogawa, Satoshi Yasuda
Journal: Circulation (2015)

Background: There have been limited data available regarding response of renal artery stenting for cardiac disturbance syndrome (CDS) in atherosclerotic renal artery stenosis (ARAS) patients. The PREMIERE registry was a multicenter, retrospective study to clarify predictors for the improvement of cardiac symptoms after renal stenting. Methods and Results: We enrolled 51 ARAS patients with CDS undergoing successful renal artery stenting (age 73.3±1.43, 30 males) from 11 hospitals in Japan between January 2000 and August 2015. The improvement of cardiac symptoms evaluated by NYHA functional class was observed in 86.3% (44 patients). According to a univariate analysis, eGFR and echocardiographic indices such as interventricular septal wall thickness (IVS) and early transmitral flow velocity were significantly (P&lt;0.05) associated with the improvement of cardiac symptoms. Stepwise multivariate analysis using those variables with P&lt;0.15 identified IVS as an independent predictor (Odds ratio 0.29; P=0.039). According to receiver operating characteristic (ROC) curve analysis, IVS cut off of 11.9 mm provided the best predictive value with a sensitivity of 78.4% and a specificity of 79.5% (Figure). Conclusion: The present multicenter, retrospective study demonstrated that echocardiographic indice of IVS was a potential clinical predicator for the improvement of cardiac symptoms after renal artery stenting.
Abstract 18904: Cardiac Arrhythmias During Long Duration Spaceflight
Authors: Jeffrey L Hastings, Jaime Kowal, James Daniels, Shigeki Shibata, Steven H Platts, Doug R Hamilton, Richard L Page, Jason Ng, Jeffrey J Goldberger, Michael W Bungo, Benjamin D Levine
Journal: Circulation (2013)

PURPOSE: Whether cardiac arrhythmias are increased during spaceflight has been a long standing question for the human space program. Few data are available from long duration flight. To evaluate the incidence of in-flight arrhythmias we studied 12 astronauts during 4-6 months on the International Space Station with high-fidelity Holter monitoring. We hypothesized that spaceflight does not increase the incidence of cardiac arrhythmias, and when arrhythmias are observed they represent a benign substrate. METHODS: Twelve astronauts (3 women) wore 48hr Holter monitors: two preflight; in-Flight Day (FD)-14, 30, 75, 135; 15 days prior to return; and immediately upon landing. Individuals recorded symptoms in a diary. Arrhythmia frequency was assessed blindly by an experienced electrophysiologist. RESULTS: Baseline data showed 125±359 (range 1-1262) supraventricular ectopic beats (SEB) per 48hr period, while in-flight recordings showed 320±1137 SEB (range 0-5405); ventricular ectopy (VEB) at baseline was 286±944 beats (range 0-3282) and 305±775 beats (range 0-3439) in-flight confirming the substantial inter-individual variability. SEB and VEB at baseline were 0.06±0.16% and 0.13 ± 0.42% of all beats respectively, while the 48hr Holter with the largest number of ectopic beats for each astronaut was 0.25±0.74% (p=0.284) and 0.24±0.51% (p=0.177) respectively, demonstrating no significant change in ambient ectopy. There were no sustained arrhythmias in flight; short runs of NSVT (all &lt;5 beats) were observed both pre and in-flight in some astronauts. Filtered QRS duration (baseline: 84.5±8.2; in-flight maximum: 90.5±12.1 msec, p&lt;0.001), and low amplitude signal duration (baseline: 23.2±6.4; in-flight maximum: 27.1±6.4 msec, p&lt;0.01) increased subtly, but remained within normal limits; root mean square voltage of the terminal 40 ms did not change (baseline: 62.5±34.3; in-flight maximum: 73.0±29.4 microV, p=0.19). T wave alternans was not present at any time. Analysis of QT variability and T wave morphology in the first 6 astronauts did not change. CONCLUSIONS: Baseline arrhythmias are quite variable between astronauts; data suggest that long duration spaceflight is not associated with changes in arrhythmia frequency or arrhythmic substrate.
Abstract 18905: Myocyte-Specific Deletion of P300 Prevents Cardiac Hypertrophy Following Pressure Overload in a Mouse Model
Authors: Jianqin Wei, Shaurya Joshi, Jing Liu, Michael Hoosien, Sumit Jain, Nanette H Bishopric
Journal: Circulation (2013)

Background: The lysine acetyltransferases CREB binding protein (CBP, KAT3A) and p300 (KAT3B) are important epigenetic regulators of gene transcription. Both share extensive sequence homology and multiple overlapping functions and properties. However, genetic loss-of-function studies indicate that CBP and p300 have distinct roles in cardiac development. We have previously shown that p300 is a stress-responsive, quantitatively limiting driver of cardiac hypertrophy. Objective: To compare the roles of p300 and CBP in adult cardiac hypertrophy. Methods: Recombination was induced in mice harboring the a-MHC Mer-Cre-Mer transgene and CBP or p300 floxed alleles with tamoxifen (TA) at 10 weeks of age. Pressure overload was induced by transverse aortic coarctation (TAC) and pressure gradients were quantitated by Doppler flow/velocity. Cardiac function was evaluated using echocardiography before and after surgery. Apoptosis and fibrosis was assessed using CardioTACs assay and Masson tri-chrome staining respectively. Myocyte hypertrophy and fibrosis were quantitated by histology at d21 post TAC. Genome-wide transcriptional analysis was performed by microarray and RNASeq. Results: TAC produced myocyte hypertrophy, cardiac enlargement, and systolic dysfunction that was reduced to near sham-operated levels in a gene-dose-dependent manner by loss of p300 (p&lt;0.001 for p300 fl/fl vs p300+/+). Loss of p300 did not impair survival post TAC. Histologically, fibrosis and myocyte apoptosis after TAC were markedly decreased in p300fl/fl vs p300+/+ mice (15.04% vs 38.92%,p&lt;0.001). Remarkably, cardiac systolic function (EF % and FS %) were unimpaired in p300KO mice following TAC. Loss of CBP had no impact on any of these parameters. Transcriptional analysis revealed that loss of CBP had a much greater impact on gene expression than loss of p300, and that relatively few genes were responsive to both p300 and CBP loss. A group of 89 mRNAs and ncRNAs were exclusively sensitive to p300 loss, reflecting an important function in oxidative stress. Conclusions: Cardiac myocyte p300 plays a critical and cell-autonomous role in cardiac hypertrophy and heart failure that is not complemented by CBP. Investigation of p300 specific gene targets is warranted.
Abstract 18928: Vorapaxar Reduces Coronary Stent Thrombosis: Results From the TRA2P-TIMI 50 Trial
Authors: Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Stephen D Wiviott, Sabina A Murphy, David A Morrow
Journal: Circulation (2013)

BACKGROUND: Vorapaxar is a novel potent antiplatelet agent that reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy. We investigated whether treatment with vorapaxar reduced the rate of coronary stent thrombosis (ST) in stable patients with atherosclerotic vascular disease. METHODS: TRA2°P-TIMI 50 was a multinational, randomized, double-blind, placebo controlled trial of vorapaxar in stable patients with prior MI, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria. RESULTS: A total of 26,449 patients were randomized with 14,042 (53%) having a history of a coronary stent implantation prior to randomization. An additional 449 patients received a coronary stent during the trial. The rate of ARC definite stent thrombosis in placebo group at three years was 1.4% (0.47% per year) in those with a coronary stent implanted prior to or during the trial (Fig 1A). Vorapaxar reduced ARC definite ST (1.1% at three years, 0.36% per year, HR 0.71, p=0.040, figure 1B). In those patients who qualified for the trial with MI (17,779, 77% on aspirin and thienopyridine), 76% had a history of prior stenting or a new stent during the trial (13,489). The rate of ST was similar (0.47% per year placebo, Fig 1A) with a consistent reduction with vorapaxar (HR 0.71, p=0.046, Fig 1B). CONCLUSIONS: The rate of ARC definite ST in stable patients with coronary stents, the majority of whom were receiving DAPT, was approximately 1.4% at three years. Vorapaxar significantly reduced ARC definite ST in stable patients with atherosclerotic vascular disease and history of coronary stent on standard antiplatelet therapy.
Abstract 18881: Improper Elastic Fiber Assembly Drives Cardiac Pathology
Authors: Elza D van Deel, Luuk te Riet, Els Moltzer, Nicole van Vliet, Lorna Fiedler, Nicky Boontje, Ellen Rouwet, Jolanda van der Velden, Michael D Schneider, Dirk J Duncker, Jeroen Essers
Journal: Circulation (2013)

Elastin is ubiquitously expressed in the cardiovascular system and essential for maintaining aortic wall integrity and function. Little is known however, about the role of elastin in the heart. To explore the influence of elastin on cardiac pathology we knocked down an essential protein for elastogenesis, fibulin-4, in human induced pluripotent stemcell (iPS)-derived cardiomyocytes. Strikingly, 90% reduction of fibulin-4 expression by shRNA, increased cardiomyocyte size by 35% and enhanced expression of atrial natriuretic peptide (ANP) and of TGFβ-regulated genes such as connective tissue growth factor and plasminogen activator inhibitor-1 in these cultured cardiomyocytes (all p&lt;0.05). Accordingly, mice with a 75% reduction in fibulin-4 expression (Fibulin-4R/R), developed cardiac hypertrophy, dilation and dysfunction (ejection fraction [76±2 to 21±3 %]) as well as aortic aneurysms. This was accompanied by elevated myocardial TGFβ signalling and ANP, while expression of sarcoplasmic reticulum calcium transport ATPase and maximal force generating capacity of single membrane-permeabilized cardiomyocytes was reduced by 60% and 25%, respectively (both p&lt;0.05). Subsequently, we explored the influence of fibulin-4 and elastogenesis on the development of cardiac pathology by subjecting mice with a 50% reduction in fibulin-4 expression (Fibulin-4+/R), without apparent cardiovascular abnormalities, to 4 weeks of transverse aortic constriction (TAC). Following TAC, mortality was markedly increased in Fibulin-4+/R animals compared to wildtype mice [20% to 84%; p&lt;0.05]. Moreover, in surviving mice, reduced fibulin-4 expression aggravated TAC-induced LV systolic and diastolic dysfunction and pulmonary congestion without affecting valvular function. In conclusion, using gradually reductions in fibulin-4 expression in mice and iPS derived cardiomyocytes we show that improper elastic fiber assembly drives cardiac pathology.