tbuckley/cabot-search huggingface dataset:
Abstract 11833: Lipid-rich Core Quantification in Carotid Atherosclerosis Using MRI T2 Mapping - Relation to Clinical Presentation and Plaque Macrophage Activation
Authors: Joshua T Chai, Luca Biasiolli, Linqing Li, Mohammad Alkhalil, Francesca Galassi, Chris Darby, Alison Halliday, Linda Hands, Timothy Magee, Jeremy Perkins, Ed Sideso, Ashok Handa, Peter Jezzard, Matthew D Robson, Robin P Choudhury
Journal: Circulation (2015)

Introduction: Non-invasive plaque lipid quantification is appealing both for treatment selection and as predictor of future plaque events. However, current MRI methods are insensitive, require a coalesced mass of lipid and rely on multicontrast acquisition. We sought to: (1) provide tissue validation of quantitative T2 maps to measure plaque lipid; and (2) investigate whether this technique could discern differences in plaque characteristics between symptomatic and asymptomatic plaques. We also hypothesised that plaque lipid content correlates with differential plaque macrophage activation. Methods: 40 patients scheduled for carotid endarterectomy were recruited for 3T carotid MRI. Lipid Area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. Plaque macrophages were procured using laser-capture microdissection from frozen tissue and subjected to microarray analysis. Results: Lipid Area (%) on T2 mapping and histology showed excellent correlation, both by individual slices (R = 0.85, P &lt; 0.001) and plaque average (R = 0.83, P &lt; 0.001). Lipid Area (%) on T2 maps was significantly higher in symptomatic compared to asymptomatic plaques (31.5 ± 3.7% vs. 15.8 ± 3.1%, P = 0.005) despite similar degrees of carotid stenosis. ROC curve analysis showed that T2 mapping has a fair to good ability to discriminate between symptomatic and asymptomatic plaques. Finally, using gene set enrichment analysis, plaque lipid content by T2 map positively correlated with distinct patterns of macrophage activation e.g. INF-STAT1 pathway (P &lt; 0.01, FDR &lt; 0.25). Conclusions: MRI T2 mapping accurately quantifies plaque lipid non-invasively. Greater plaque lipid content was found in symptomatic plaques; and this correlated with inflammatory pathway activation in plaque macrophages. This new technique may find a role in determining optimum treatment e.g. providing an indication for intensive lipid-lowering, or anti-inflammatory therapy.
Abstract 18391: Cardiac Magnetic Resonance Imaging for the Functional Assessment of Normal Bioprosthetic Mitral Valves: A Comparison Against in vitro Flow Transducer and Doppler Echocardiography Measurements
Authors: Dimitrios Maragiannis, Matthew S Jackson, Stephen R Igo, Karen Chin, Kyle Autry, Mohamad Ghosn, Dipan Shah, Stephen H Little
Journal: Circulation (2013)

Introduction: Few studies have evaluated the accuracy of Cardiac Magnetic Resonance (CMR) imaging for the functional assessment of bioprosthetic mitral valves (BMV). This study aimed to compare CMR measurements of flow volume and orifice area against in vitro flow transducer and Doppler Echo measurements. Methods: A previously described pulsatile, MRI compatible flow loop was used to generate diastolic flow volumes (DFV) across BMVs (sizes 27, 29, and 31 mm) within a “cardiac” imaging chamber. The imaging chamber was placed within a 1.5 Tesla MRI scanner (Siemens) under DFVs of 70, 90 and 110 ml/beat at 70 bpm. Steady state free precession sequences were used to assess BMV morphology and motion. 2D Phase contrast (PC) pulse sequences were used to assess trans-valvular velocity and mean stroke volume. Anatomic orifice area (AOA) and the effective orifice area (PC-EOA) were measured by 2 independent observers. A 1-5MHz ultrasound probe (iE33, Philips) was used to evaluate trans-valvular inflow velocity and Doppler-EOA. Results: For bioprosthetic valves, PC-CMR techniques accurately measure forward stroke volume across the range of predefined reference flow volumes (N=10; r=0.99, p&lt;0.001, mean difference 3.5±3.4 ml/beat). PC-CMR peak velocity showed good correlation with Doppler derived values (r=0.91, p&lt;0.001, mean difference -14.5±14.1 cm/s). CMR-derived AOA and PC-EOA correlated well with each other (r=0.87, p&lt;0.05, mean difference 0.04±0.1 cm2). However, CMR-derived AOA and PC-EOA correlated poorly with Doppler derived EOA (r=0.6, p=0.0067, mean difference 0.9±0.17 cm2). Conclusion: PC-CMR is a promising modality for determining DFVs and assessing velocity through competent BMVs directly at the valve itself. This is inherently different than the normal clinical MRI practice of inferring valvular flow volumes from indirect measurements of aortic flow and ventricular dimension changes.This method could prove useful for regurgitant flow measurement.
Abstract 11929: Simultaneous Assessment of Myocardial Viability With <sup>18</sup> F-fluorodeoxyglucose Uptake and Late Gadolinium Enhancement by PET/MRI
Authors: Atsuro Masuda, Takayoshi Yamaki, Hiroyuki Kunii, Takeyuki Nanbu, Takamitsu Hara, Hitoshi Kubo, Hiroshi Ito, Seiichi Takenoshita, Yasuchika Takeishi
Journal: Circulation (2016)

Introduction: Both 18 F-fluorodeoxyglucose (FDG) PET and late gadolinium enhancement on cardiac MRI (LGE-CMR) have been utilized for myocardial viability evaluation. However, the association between these 2 modalities has not been fully investigated. The aim of this study was to compare FDG PET and LGE-MRI findings simultaneously using an integrated PET/MRI. Methods: Twelve participants (age 68.8 ± 7.9 years old, 11 males, left ventricular ejection fraction 40.5 ± 15.0%) with old myocardial infarction were enrolled. Total 204 segments were analyzed according to the 17-segment model. FDG PET/MRI was performed for each participant under hyperinsulinaemic-euglycemic state. The FDG uptake was semiquantitatively measured as %uptake. The transmural extent of LGE-CMR was evaluated by a 5-point scoring system (0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100%). Left ventricular (LV) wall thickness at end-diastolic phase and LV wall thickening were also measured by CMR. Viable myocardium was defined as less than 50% of the transmural extent of LGE-CMR. Results: Relative FDG uptake and the transmural extent of LGE-CMR were significantly correlated (P &lt; 0.0001, Spearman ρ = -0.63). Relative FDG uptake was correlated with LV wall thickness (P = 0.003, ρ = 0.22) and LV wall thickening (P &lt; 0.0001, ρ = 0.59). Receiver operating characteristic analysis demonstrated that the best cut-off value of FDG uptake to predict myocardial viability was 63% (area under the curve 0.90). When the cut-off value set to 63%, sensitivity was 81.6%, specificity was 80.8%, and accuracy was 81.4%. Conclusions: Relative FDG uptake was comparable to the transmural extent of LGE-CMR in assessing myocardial viability. Simultaneous evaluation using the integrated PET/MRI is feasible and may provide novel insights into evaluation of the myocardial viability.
Abstract 18323: Positive Frequency-Dependent Effects of Highly Selective Kv1.5 Blockers (XEN-D0103 &amp; MK-0448) in Right Atrial Trabeculae From Patients in Sinus Rhythm
Authors: Simone Loose, Judith MÜller, Erich Wettwer, Said El-Haou, Claire Jackson, Raymond Tang, James Milnes, Ursula Ravens, John Ford
Journal: Circulation (2013)

Aim: Despite promising effects of Kv1.5 blockers in experimental models of atrial fibrillation, limited data is available for man. Therefore we investigated two selective Kv1.5 channel blockers, XEN-D0103 and MK-0448, on atrial myocardium from patients in sinus rhythm (SR). Method: Kv1.5 currents were measured with in CHO cells expressing hKv1.5. Sharp microelectrodes were used to record action potentials (AP) at various stimulation frequencies (37°C) in right atrial trabeculae from consenting patients in SR. Results: Kv1.5 was activated by voltage-clamp steps from -80 to 0mV (900ms)at 0.2Hz (room temp). XEN-D0103 and MK-0448 inhibited Kv1.5 with IC50 of 25nM and 32nM resp.. Both compounds display &gt;500-fold selectivity over hERG, Kv4.3, Nav1.5, Cav1.2, Kir2.1. The plateau phase of the atrial AP was elevated with XEN-D0103 and MK-0448 in a concentration-dependent manner. At 1Hz this effect was associated with shortening of APD90 and of effective refractory period (ERP) (see Table). At higher stimulation rates the APD90 and ERP shortening effects of XEN-D0103 and MK-0448 (3μM each) diminished and eventually converted to prolongation. With XEN-D0103, significant prolongation of APD90/ERP occurred at 3Hz and higher rates. In control, 10 out of 16 trabeculae followed stimulation at 5Hz, however, in the presence of XEN-D0103 10 out of 10, and with MK-0448 4 out of 6 preparations failed to capture stimulation. Conclusion: This is the first report of robust frequency dependence of selective Kv1.5 channel blockers in human atrial myocardium suggesting that these drugs are more effective at high than at low activation rates. Therefore, XEN-D0103 and MK-0448 should possess potential for suppressing episodes of rapid atrial excitation. Table: Frequency-dependent effects of the Kv1.5 blockers XEN-D0103 and MK-0448 in human right atrial trabeculae. Differences between pre-drug controls and values after 1 hour of drug superfusion (means ± SEM).
Abstract 18420: Angiotensin II Infusion Provokes Remodeling of the Aortic Valve Tissue in Mice: A Model for Early Non-Calcified Stage of Aortic Sclerosis
Authors: Paolo Poggio, Emanuela Branchetti, Juan B Grau, Joseph E Bavaria, Robert C Gorman, Giovanni Ferrari
Journal: Circulation (2013)

Objective: Asymptomatic aortic valve (AV) sclerosis, characterized by thickening of the cusps with accumulation of reactive oxygen species (ROS) and ECM remodeling, is a hallmark of several cardiovascular conditions. Despite its high prevalence, there is a lacking of reliable animal models for early non-calcified stages of aortic sclerosis. Our preliminary data show that infusion of Angiotensin II in mice receiving a Western diet augments atherosclerosis and causes formation of aortic aneurysms (AA). Although AV disease and atherosclerosis are independent dysfunctions, early stages of these conditions share many similarities. We tested, in vivo, whether Ang II infusion would induce changes in aortic valve microstructure. Methods: Male wild type mice were fed with Western diet and infused with saline (n=5), or Ang II (1 mg/kg/min) (n=15) for 28 days. Echocardiographic and immunohistological analysis were performed on each animal to test AV thickness, ROS accumulation and ECM remodeling. Results: We reported the development of aortic aneurysms in 54% of the experimental group compared to the controls, independent from changes in blood pressure (FIG 1A). Interestingly, microdissection analysis of the aortic valve of all mice receiving Ang II show increased cusp thickness (FIG 1B) when compared to saline infused mice (p&lt;0.01). Histological and protein quantification analysis also revealed increased ROS (nitrotyrosine staining) in mice cusps (FIG 1C) and ECM remodeling without affecting the mechanical proprieties of the valve. Conclusion: Here we conclude that our animal model mimics the tissue remodeling of the aortic cusps with increased thickness and accumulation of reactive oxygen species as seen in human pathological samples of aortic sclerosis. FIG 1. Ang II infusion and AV thickness. (A) Example of Ang II-induced AA, TTE and AA expansion (B) Representative images of H&amp;E of AV cusp ± Ang II with cusp’s thickness (B) Nitrotyrosine staining and quantification.
Abstract 18372: Platelet Reactivity Measurements Before and After Percutaneous Coronary Intervention Among Patients Undergoing Early Invasive Management for Acute Coronary Syndrome
Authors: Leonardo Carvalho, Chin Chee Tang, Teo Zhen Long, Bryan Yan, Xu-Rui Huang, Richard Troughton, Alan Fong, Melissa Mejin, Chloe Ting, Mingxue Jing, Kylie Kong, Ronald Lee Chi Hang, Boon Lock Chia, Huay Cheem Tang, Arthur Mark Richards, Mark Chan
Journal: Circulation (2013)

Introduction: There are conflicting data on the optimal timing of platelet reactivity (PR) measurements to identify patients at risk of major adverse cardiovascular events (MACE) and bleeding. Hypothesis: We hypothesized that significant changes in PR occur peri-PCI Methods: We studied 395 patients undergoing PCI for NSTEMI/UA. Patients received, in the emergency room, aspirin (300 mg loading dose followed by 100 mg maintenance dose) and one of two P2Y 12 antagonists: clopidogrel (300 mg/ 75 mg OM) or ticagrelor (180 mg/ 90 mg BD). Adenosine diphosphate-induced multiple electrode aggregometry (Multiplate ®) was performed to analyze PR at the time of PCI and post-PCI (24 hours). In-hospital and 30-day MACE, defined as cardiovascular death, recurrent MI, stroke or stent thrombosis, and bleeding, defined as bleeding academic research consortium (BARC) type 2 or greater bleeding, were assessed in all patients. Results: Patients were treated with clopidogrel [N=356 (89%)] or ticagrelor [N=39 (11%)] (Table1). The mean pre and post PCI PR was consistently higher with clopidogrel than ticagrelor. However, the mean reduction in pre-post PCI PR was 3-fold greater for clopidogrel than ticagrelor (P&lt;0.01 by Kruskall-Wallis test). In-hospital and 30-day post-discharge MACE and bleeding events corresponded closely with the frequency of pre and post PCI hyporesponders, defined as PR &gt;468 AU*min, and hyperresponders, defined as PR &gt; 300 AU* min, respectively. Conclusion: Large differential reductions in PR were observed within 24 hours post-PCI. PR measurements tracked well with inhospital and post-discharge MACE and bleeding events. Among patients with only pre-PCI measurement, consideration should be given to repeating PR measurements within 24 hours post-PCI.
Abstract 12145: Remote Ischemic Preconditioning Regulates Post-resuscitation Microcirculation via A K <sub>Atp</sub> Channel-dependent Mechanism in a Rat Model of Cardiac Arrest
Authors: Shen Zhao, Ziren Tang, Jiangang Wang, Zhengfei Yang, Feng Chen, Mary A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: Remote ischemic preconditioning (RIPC) provides potent protection to tissue microcirculation against ischemic-reperfusion injury. However, the underlying microvascular mechanism of RIPC is not fully understood. The present study investigated whether the protective effects of RIPC on microcirculation and myocardial function after cardiopulmonary resuscitation (CPR) are related to K ATP channel activation. Hypothesis: RIPC-induced activation of the K ATP channel would result in improved microcirculation and myocardial function following resuscitation. Methods: Twenty-four male Sprague-Dawley rats were randomized into three groups (n=8 for each group): RIPC, RIPC with K ATP channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by 5 minutes of reperfusion. Ventricular fibrillation was induced and untreated for 8 min followed by 8 min of CPR. The animals were monitored for 6 h and observed for an additional 66 h. Sublingual microcirculation was assessed by a sidestream dark-field imaging device, and myocardial function was measured by echocardiography at baseline, 30 min, 1 h, 2 h, 4 h, and 6h post-resuscitation. Results: At 30 min and subsequent intervals post-resuscitation, both perfused vessel density and microcirculatory flow index were significantly greater in the RIPC group than in the control group ( P &lt; 0.05). Compared with the control group, a significantly higher ejection fraction, myocardial performance index, and greater duration of survival were observed in the RIPC group ( P &lt; 0.05). Pretreatment with the K ATP channel blocker (glibenclamide) significantly reversed the microvasucular and myocardial protective effects of RIPC ( P &lt; 0.05) (Figure 1, 2). Conclusions: In a rat model of CPR, the beneficial effect of RIPC on sublingual microcirculation and cardiac function with improved survival was related, at least in part, to the activation of K ATP channel.
Abstract 18458: Cardiac Magnetic Resonance T1 Mapping Identifies Diffuse Ventricular Fibrosis in Patients With Atrial Fibrillation Undergoing First and Repeat Catheter Ablation
Authors: Omair Yousuf, Roy Beinart, Irfan M Khurram, Songtao Liu, David A Bluemke, Jane DeWire, Stefan Zimmerman, Hugh Calkins, Saman Nazarian
Journal: Circulation (2013)

Background: Left ventricular (LV) T1 mapping by cardiac magnetic resonance (CMR) imaging may quantitatively identify diffuse LV fibrosis in patients with atrial fibrillation (AF). An inverse relationship between T1 relaxation times after gadolinium and degree of LV fibrosis is hypothesized. The primary aim of this study was to compare LV T1 times amongst healthy volunteers, patients undergoing first time catheter ablation for AF, and patients undergoing repeat ablation for recurrent AF. Methods: CMR imaging at 1.5-Tesla was performed in patients with symptomatic AF before ablation and in healthy volunteers. A modified Look-Locker inversion-recovery (MOLLI) sequence (11 images within 17 heartbeats) was acquired in the vertical long axis plane 12 min after gadolinium chelate (0.20 mmol/kg). T1 measurements were obtained from the inferoposterior LV myocardial wall. Results: 51 patients (64% males, median age 55 years, inter-quartile range [IQR] 51-65 years) (53% prior to first ablation, 47% prior to repeat ablation) and in 16 healthy volunteers (31% males, median age 26 years, IQR 23-30 years) were evaluated. The median LV T1 relaxation time was lower in patients with AF undergoing first ablation (454ms, IQR 412-474ms) and recurrent ablation (431ms, IQR 412-464ms) compared to healthy volunteers (595ms, IQR 566-606ms, P&lt;0.001) [Figure]. In an ordered logistic regression model, T1 time remained associated (p=0.044) with participant status (control, prior to first ablation, prior to repeat ablation) as the dependent variable, after adjusting for age, gender, BMI, and DM. Conclusion: Post-gadolinium ventricular T1 mapping identifies diffuse LV fibrosis in AF patients undergoing first and repeat catheter ablation. Lower T1 times were observed in patients who had prior ablation attempts, suggesting greater LV fibrosis in those with recurrent AF. Further studies will be needed to determine changes in T1 time after restoration of sinus rhythm with catheter ablation.
Abstract 18639: Ventricular Tachycardia Events Are Associated With Admissions for Infection or Heart failure in Patients With Left Ventricular Assist Devices and Implantable Cardio-Defibrillators
Authors: Thomas J ONeill, Jason N Katz, Sarah Waters, Amanda Bowen, Kimberly Guise, Eugene Chung, Anil Gehi, Brian C Jensen, Patricia Chang, John P Mounsey, Jennifer Schwartz
Journal: Circulation (2013)

Background: Left ventricular assist devices (LVAD) have dramatically affected the treatment of end stage heart failure (HF), however preventing readmissions remains critical to optimize patient quality of life. Following LVAD implantation, pts are readmitted most commonly for infection, HF, arrhythmia and anemia. We designed a novel implantable cardio-defibrillator (ICD) programming protocol for pts with LVADs and ICDs to maximize ventricular arrhythmias (VA) detection and minimize shocks. We hypothesized that increasing detection of VA in LVAD pts may reduce readmission rates. Methods: Forty-two pts at UNC with an LVAD and ICD underwent reprogramming. The protocol included: ventricular fibrillation &gt;220 bpm; ventricular tachycardia (VT) &gt;185 bpm with 12 bursts of ATP then a single shock; VT monitor &gt;150 bpm. Device interrogations were performed at LVAD clinic follow up, for symptoms, and at the time of readmission. Data was collected with an approved institutional IRB. Results: During an average follow up of 11.3 months before and 7.4 months after reprogramming, there were 53 unplanned admissions (21 admissions after ICD reprogramming). After reprogramming 5 admissions (23% - 1438 patient-days/admit) were for HF or VA. Prior to reprogramming there were 15 HF/VA admissions (728 patient-days/admit). After reprogramming 4 admissions (18%) were for bacterial infections (5 prior to reprogramming). The remaining were primarily for anemia (17%) or neurologic symptoms (36%). After reprogramming, arrhythmias were detected on ICD interrogation in 3 of 5 HF and 2 of 4 bacterial infection admissions. 40% were due to sustained VA &gt;10 sec and 60% were due to supraventricular tachycardia. By comparison 0/13 of the other admissions had documented ICD arrhythmias. Conclusions: Following implementation of a novel ICD programming protocol to increase detection of VA, there was a marked decrease in admissions for cardiac diagnoses. ICD interrogations found VA events were associated with admissions for HF and infection. HF and infections may cause hemodynamic perturbations that result in arrhythmias detected by ICDs with appropriate programming. Our data suggests that ICD data may augment available techniques to assess and triage this patient population.
Abstract 18686: Serial Two Dimensional Echocardiographic Observations and Measurements Obtained by Fetal Echocardiograms: Correlation With Gestational Age
Authors: Xiaoyan Gu, Yihua He, Ye Zhang, Jiancheng Chen, Ying Zhao, Xiaowei Liu, Yong Guo, Jiaoyang Chen, Zhongshan Guo, Zhian Li
Journal: Circulation (2013)

Objective: The purpose of the study was to establish changes that may occur between 20 and 34 weeks of pregnancy in linear measurements of the cardiac chambers, great vessels, aortic isthmus, descending aorta and foramen ovale by fetal echocardiography (FE). Regression analysis was utilized to determine any possible correlation between the linear measurements and gestational age. Methods: Serial FEs were obtained on 2573 normal single pregnancies with accurate gestational ages. FEs obtained using ASE guidelines were divided into 15 groups according to gestational age. Results: Measurements of thoracic diameter, total cardiac diameter, left atrial (LA) and right atrial (RA) diameters, left ventricular (LV) and right ventricular (RV) diameters, and aortic and pulmonary artery diameters significantly increased between 22 and 28 weeks (p &lt; 0.01). Aortic arch isthmus (AoAI), descending Ao diameter, left and right pulmonary artery (PA) diameters and foramen ovale diameter did not change significantly. Between 20 and 34 weeks of pregnancy, RA and RV diameters were always greater than LA and LV diameters, the PA diameter was always greater than Ao diameter, and the AoAI diameter was always greater than the ductal artery (p &lt; 0.01). The ductal artery diameter was always greater than left and right PA Regression analysis between FE dimensions and gestational age showed a significant progressive increase in thoracic and total cardiac diameters, LA and RA diameters, LV and RV diameters, AoAI and descending Ao diameters and ductal artery diameter. Conclusion: FE can accurately assess cardiac structure and is capable of establishing normal reference values of cardiac and great vessel anatomy. As expected, most measurements statistically increase with increasing gestational age.