tbuckley/cabot-search huggingface dataset:
Abstract 281: Traumatic Brain Injury Accelerates Onset of Hypotension with Less Blood Lost in a Pressure-Guided Model of Polytrauma with Uncontrolled Hemorrhage by Aortic Tear
Authors: Nathan J White, Xu Wang, Nicole Bradbury, Susan Stern
Journal: Circulation (2011)

Objective: Traumatic brain injury (TBI) is thought to exacerbate the severity of hemorrhagic shock by interfering with compensatory neurovascular reflexes. However, this effect remains undefined. We use a swine model of uncontrolled hemorrhage by aortic tear to examine the effect of TBI on blood pressure and blood loss during shock. We hypothesize that TBI accelerates onset of hypotension during hemorrhage with less blood lost. Methods: Anesthetized domestic swine were hemorrhaged at a controlled rate by arterial catheter to mean arterial pressure (MAP) of 30mmHg and maintained for 15 minutes. Aortic tear allowing free bleeding was made when MAP = 50 mmHg during initial catheter hemorrhage. TBI was achieved by a fluid percussion device applied directly to the Dura just prior to hemorrhage. Time intervals to goal MAP, catheter hemorrhage volumes, and metabolic parameters were recorded during the hemorrhage and shock periods. A control group without TBI was similarly instrumented and hemorrhaged for comparison. Variables were compared in animals with and without TBI using T-tests and associations were examined using correlation. Results: N= 30 swine weighing mean (SD) 27(3.4) kg were compared (21 with TBI vs. 9 without TBI). The TBI group achieved goal MAP=30mmHg after aortic tear significantly faster (TBI= 1.0 min vs. No TBI=1.9 min, p=0.016). The TBI group required significantly less additional blood withdrawn to maintain goal MAP during the 15 minute shock period (TBI= 5.8ml/kg vs. No TBI=11.6ml/kg, p=&lt;0.0001). Yet, lactate accumulation was similar between groups (TBI= 4.7mmol/l vs. No TBI=4.4mmol/l, p=0.68). Mean percussive pressure at the Dura = 3.4(0.4) atm in the TBI group. Dural pressure was positively associated with rate of blood pressure change to MAP=50mmHG (R=0.41, p=0.026) and with total lactate concentration at the end of the shock period (R=0.55, p=0.002). Conclusion: In this model, animals with TBI demonstrated an altered blood pressure response to hemorrhage. Current guidelines for estimating blood loss using blood pressure may not apply in the setting of hemorrhagic shock with TBI.
Abstract 24: Postresuscitation Care Practices Following Cardiac Arrest at 6 Regional Interventional Cardiology Centers in the United States, 2007-2011
Authors: David Seder, Michael Mooney, Nainesh Patel, John McPherson, John McMullen, Karl B Kern, Barb Unger, J Browning, S Nanda, Melkon Hacobian, M B Kelley, Niklas Nielsen
Journal: Circulation (2011)

Background: We characterized post-resuscitation care practices in cardiac arrest (CA) survivors at six regional PCI centers in the United States. Methods: Demographics, hospital course, and treatments of 663 cardiac arrest survivors were retrospectively and prospectively entered into a secure, web-based registry (INTCAR). Interhospital variability was evaluated, and group practices compared to AHA guidelines. Results: Mean age was 61 (+14.9) years, 69.2% male, 58.8% VT/VF, 23.5 (+16.3) minutes from arrest to return of spontaneous circulation (ROSC), 31.1% had shock and 26% STEMI at admission. 50% patients were received in transfer, at estimated mean distance of 37.2 miles and 72.4 (+26.6) minutes from initial ED presentation to destination. Overall, 38.6% underwent urgent cardiac catheterization and 20.2% urgent PCI. 98% patients received therapeutic hypothermia (TH), using a surface cooling device (98.6%), cold fluids (18%), ice packs (29.7%), or an intravascular cooling device (1.2%). 74.9% patients received neuromuscular blockade during hypothermia. Mean time from ROSC to initiation of TH was 178 (+142) minutes, and ROSC to target temperature 375 (+197) minutes. The highest volume center had shorter time from ROSC to onset of therapeutic hypothermia (97+87 vs 178+142 minutes, P&lt;0.001) and target temperature (314+346 vs. 375+197 minutes, P&lt;0.001) than the group mean. 15.5% patients underwent MRI, 41.7% head CT, 33.6% continuous EEG monitoring, 16.5% IABP, and 9.5% AICD placement. Urgent coronary angiography at admission varied from 15-58%; this and other differences in treatment were incompletely explained by case mix (% STEMI admissions). Conclusions: Standard post-resuscitation care practices approximated AHA guidelines for comprehensive cardiac arrest centers, but with substantial variability of practice among institutions. Where such variability exists, such as the utilization of urgent coronary angiography and revascularization in unresponsive patients at the time of hospital admission, future research should scientifically define best practices.
Abstract 18965: Monitoring the Asymptomatic Patient with Severe Mitral Regurgitation: Do Measuring LV Volumes Make a Difference in Predicting Mortality?
Authors: Sunil Penesetti, Salvatore Costa, Ronald Chin, Mandeep Sidhu
Journal: Circulation (2012)

Background: The ACC/AHA Valvular Heart Disease Guidelines include a class I recommendation for surgery in asymptomatic patients with chronic severe mitral regurgitation (MR) if the EF is ≤ 60% and/ or the end-systolic diameter (ESD) &gt; 40 mm. However, the ESD has inherent limitations because it only detects changes in one dimension while LV volume can detect subtle changes in LV geometry in multiple dimensions. We sought to measure the impact of shifting from ESD to end systolic volume (ESV) in predicting mortality. Methods: We performed a retrospective search of our single center echocardiography database over a 5 year period for all cases with severe (4+) MR. From this list of 240 patients, we reviewed the medical records to identify the subgroup of patients who remained asymptomatic at the time of echo evaluation (N = 61). Since the ACC/AHA Guidelines recommend surgical referral for asymptomatic patients with an EF ≤ 60%, these patients were also excluded in order to isolate the impact of LV size on mortality. This resulted in a total of 31 study subjects. Study subjects were classified according to 2 different methods: “classic” LV size criteria (ESD &gt; 40mm) or “volume” LV size criteria (ESV ≥ “mildly dilated” per ASE Chamber Quantification Guidelines). Volumes were obtained using a biplane Simpson. Results: As compared to classic LV size criteria using ESD, a change to volume criteria using ESV would significantly increases the percentage of patients identified with abnormal LV geometry (61% vs 25%, p &lt; 0.01). However, despite identifying a larger number of patients with abnormal LV geometry, the difference in mortality using volume criteria or classic criteria was not significant. Conclusion: Although there are conceptual advantages to the assessment of LV size using LV volumes rather than 2D linear measurements, the difference in the two methods for predicting mortality in the context of asymptomatic MR with normal EF was not significant. Further refinements in the assessment of LV volumes, larger studies, and inclusion of additional end-points such as CHF admissions may be needed to further understand the relationship between changes in LV geometry and adverse events in this population.
Abstract 18495: Loss of Syndecan-1 Results in De-differentiation of Vascular Smooth Muscle Cells
Authors: Somali Chaterji, Christoffer Lam, Rishi Goel, Aaron B Baker
Journal: Circulation (2012)

Introduction: Vascular smooth muscle cells (vSMCs) display a wide phenotypic continuum, altered during the vascular remodeling process in disease or following injury. The phenotypic state of vSMCs, modulated by the cellular microenvironment, can range from a highly proliferative, extracellular matrix-synthesizing phenotype to a highly differentiated, contractile phenotype. Syndecans, heparan sulfate proteoglycans serving as cell surface co-receptors, have emerged as powerful and complex regulators of cell function. However, the ability of syndecan-1 to regulate vSMC differentiation is not yet known. Hypothesis: We hypothesized that syndecan-1 is a regulator of vSMC phenotype and can consequently regulate the pathophysiology of disease or vessel wall restenosis. Methods and Findings: To test our hypothesis, we performed gene and protein expression studies for wild-type (WT) and syndecan-1 knockout (S1-KO) mice-derived primary vSMCs. Real time RT-PCR (n=4) indicated higher levels of smooth muscle α-actin (α-SMA), calponin, myosin heavy chain (MYH) II, and desmin, and, lower levels of the embryonic form of smooth muscle MYH in WT relative to S1-KO cells, both in low serum vSMC growth medium and in differentiation medium with heparin and transforming growth factor-β1. Higher α-SMA and calponin levels were corroborated using Western blots and immunocytochemical studies. Mechanistic studies involving the serine/threonine kinase Akt (involved in vSMC survival and differentiation) and the mTOR downstream target p-S6 ribosomal protein (p-S6RP) indicated that p-Akt tripled and p-S6RP halved in WT cells (n=3). Integrated morphometric analysis indicated that S1-KO cells were 3 times larger area-wise, more circular, and less elongated, compared to WT. Further, S1-KO cells were about 1.5 times as proliferative as WT (n≥3). Immunocytochemical assessments to evaluate the effect of syndecan-1 knockout on syndecan-1 binding proteins indicated that syntenin, cortactin, and vinculin were present in significantly higher amounts in WT compared to S1-KO cells. Conclusion: Taken together, our results support a positive role for syndecan-1 in promoting vSMC differentiation, reducing the chances of intimal hyperplasia after vascular injury.
Abstract 18456: Morphologic Predictors of Aortic Growth in Conservatively Treated Type B Aortic Dissection
Authors: Jip L Tolenaar, Frederik H Jonker, Joost A van Herwaarden, Hence Verhagen, Frans L Moll, Bart E Muhs, Santi Trimarchi
Journal: Circulation (2012)

Purpose: Conservative management of acute type B aortic dissection (ABAD) is often associated with aortic enlargement during follow-up, increasing the risk of aortic rupture. The goal of this study was to investigate whether morphologic characteristics of the dissection can predict annual aortic growth. Methods: All conservatively managed type B dissection patients of four referral centers were included (2000-2010). Aortic diameters were measured at 5 levels on the baseline and last follow-up CTA, and annual aortic growth rates were calculated for all segments. Linear regression was used to study the influence of aortic morphologic characteristics on aortic enlargement. Results : Sixty-two patients were included (41 male; mean age 60.3 ± 10.7 years). Among the 310 analyzed segments, 248 (80.0%) were dissected of which 211 (85.1%) showed aortic growth. Overall, the mean diameter increased from 36.1 ± 9.4 mm to 40.2± 11.1mm (p &lt; 0.001) corresponding with a mean aortic growth of 3.1 ± 6.3 mm/year. Multivariate linear regression analysis showed male gender (95% CI 0.84 - 4.27; p = .004), detection of entry tears (95% CI 0.32 - 8.01; p = .034,) and a saccular false lumen (95% CI 1.50 - 7.28: p = .003) were associated with a significantly increased aortic growth rate. Increasing age (95% CI -0.24 - -0.5; p = .003), false lumen located on the convexity (95% CI -4.56- -0.64; p = .009) and a circular configuration of the true lumen (95% CI -5.04 - -0.02; p = .048) were associated with a decreased aortic growth rate. Conclusions: Age, gender, saccular false lumen, detection of entry tears, the presence of the entry tear in the oncavity of and configuration of the true lumen, appear to affect aortic growth rates in conservatively treated ABAD patients. Assessment of these characteristics may be useful in the selection of ABAD patients who might benefit from closer radiologic surveillance or early intervention.
Abstract 18551: The Detection of Diastolic Stunning by Two-Dimensional Speckle Tracking Imaging Improves Initial Diagnosis in Emergency Department Patients with Suspected Acute Coronary Syndromes
Authors: Katsuhisa Ishii, Takahiro Nagai, Akihiro Komasa, Atsuko Furukawa, Eiji Tada, Kazuaki Kataoka, Yutaka Seino
Journal: Circulation (2012)

Background: Differential diagnosis of chest pain (CP) in emergency department (ED) is important for the management of acute coronary syndrome (ACS). Regional left ventricular (LV) diastolic dysfunction or diastolic stunning (DS), detected by strain image (SI) derived from two-dimensional speckle tracking technology, may persist after an episode of transient severe myocardial ischemia. We studied the incremental value of the detection of diastolic stunning by SI over the initial diagnosis (InDx) of CP in the ED for identifying patients with ACS. Methods: Consecutive 128 patients (75 men, 61 ±13 years) with CP consistent with ACS were enrolled. SI (ARTIDA, Toshiba) was acquired in the apical long-axis, two- and four-chamber views within 6 hrs in ED. Transverse strain curves were obtained and peak values of strain at the closure of aortic valve (A) and at the one third of diastolic duration (B) were measured. The SI-diastolic index (SI-DI) was determined as (A-B)/A×100% and used to identify regional LV DS. In the 40 normal subjects the SI-DIs were 76.5±10.6, 80.7±8.4, 79.4±11.6 % in the territories of the left anterior descending branch (LAD), the left circumflex branch (LCX) and the right coronary artery (RCA), respectively.Clinical evaluation, serial ECGs, and troponin (Tn) were performed in all patients, with coronary angiography (CAG) performed as clinically indicated. The InDx or “definite ACS” (D-ACS) was based on presenting CP, ECG and Tn. Final diagnosis of D-ACS was defined as elevated Tn and significant disease on CAG (&gt;50% stenosis). Results: 57 patients were diagnosed as having D-ACS. Regional LV DS (SI-DI&lt;40%) had been detected in the perfusion territories of the coronary arteries with culprit lesions in 52 (91%) of D-ACS, whereas it had been noted in 9 (13%) of chest pain syndrome (CPS). SI-DIs were 25.8±15 (n=75), 17.5±14 (n=36), 21.1±11 % (n=14) in the culprit lesions of LAD, LCX and RCA, respectively, and 70±13% (n=217) in the segments corresponding to the non-culprit lesions. For D-ACS, quantitative SI plus InDx increased sensitivity by 28% to 95% (P&lt;0.01), and non-significantly increased NPV by 21% to 97%. Conclusion: Adding the detection of regional LV DS by SI to InDx in ED increased sensitivity and NPV for detecting D-ACS.
Abstract 18476: Are Cardiac Magnetic Resonance Patterns Associated with Adverse 18-Month Outcome in Patients with Acute Myocarditis?
Authors: Francesca Sanguineti, Melina Mana, Thomas Hovasse, Yves Louvard, Thierry Unterseeh, Philippe Garot, Marie-Claude Morice, Jérôme Garot
Journal: Circulation (2012)

Introduction: Cardiac Magnetic Resonance (CMR) is a fundamental tool in the diagnosis of Acute Myocarditis (AM). However, its prognostic value is not well established. Hypothesis: CMR findings in patients with AM may predict functional/clinical outcome. Methods: We studied consecutive pts diagnosed with AM by CMR between 2008 and 2011. All pts underwent initial clinical assessment and CMR was performed at a mean of 11±12 days after acute clinical presentation. Black-blood T2-CMR was used for myocardial edema assessment and contrast-enhanced CMR was performed 3 (early gadolinium enhancement, EGE) and 10 (late gadolinium enhancement, LGE) min after gadolinium chelates. Images were analysed dividing the myocardium into 17 segments and 3 myocardial sectors (subepicardium, midwall, and subendocardium), allowing quantification of lesions extent as percent of LV myocardium. Presence of pericardial effusion and LV segmental wall motion was assessed. Adverse cardiac events including recurrence of symptoms, congestive heart failure, ventricular arrhythmias, heart transplantation, or death, were carefully recorded at clinical follow-up (FU) performed 19±8 months after indexed CMR. Results: The patient population comprised 203 pts (43±17 year-old, 76% males) with AM. A total of 22/203 patients (10.8% of the whole population) experienced adverse cardiac events. By univariate analysis, the extent of EGE was inversely correlated with the presence of clinical events at FU (2.2±4.1 vs. 5.1±6.0% of LV myocardial mass, for pts with and without adverse cardiac events, respectively, p=0.005). Additionally, pts with altered EF on initial CMR examination had worse myocardial function at FU. In contrast, presence of hyper-T2 signal (p=0.68), extent (p=0.72) and distribution (p=0.09) of LGE, presence of pericardial effusion p=0.18), were not associated with adverse clinical outcome. Multivariate analysis showed no CMR predictors of adverse clinical outcome. Conclusions: In this large cohort of patients with AM, there were no CMR predictors of adverse clinical outcome. A significant association was found between initial LV function and impaired LVEF at FU, as well as between EGE and adverse clinical events.
Abstract 18544: Geometry and Function of Left Ventricle and Mitral Valve After Surgical Repair of Submitral Left Ventricular Aneurysms Assessed with Multi-slice Computed Tomography
Authors: Adam J Penkalla, Natalia Solowjowa, Michael Dandel, Miralem Pasic, Yuguo Weng, Roland Hetzer, Christoph Knosalla
Journal: Circulation (2012)

Objectives: Surgical repair of submitral aneurysms presents a technical challenge especially if the mitral valve (MV) apparatus is involved. We present our single center surgical experience and the potential of multi-slice computed tomography (MSCT) in the assessment of aneurysm morphology and changes in MV and LV geometry. Methods: In 05/06-04/12, 21 patients (m:w=17:4, ages 39 to 78, mean 63 yrs; mean NYHA class 2.8) with submitral LV aneurysm were operated upon. Echocardiography and MSCT (Somatom Definition, Siemens) were performed before and after surgery. LV and aneurysm end-diastolic/end-systolic volume were measured and indexed to body surface area (LV-EDVI/LV-ESVI, A-EDVI/A-ESVI). LV ejection fraction (LVEF), cardiac output (CO) and cardiac index (CI) were calculated on the basis of MSCT data. MV geometry was characterized by mid-systolic coaptation distance (CD), tenting area (TA) and MV closure angle (MVCA). Results: Thirty-day and 5-year survival was 88.9%±7.4% and 82.1%±9.5%. Aneurysms were localized in myocardial segments 4/10/11. Preoperative A-EDVI showed a slight systolic increase, demonstrating adverse volume shift. There was reduction of LV-EDVI (141.4±21.6 to 72.7±12.9 ml/sqm, p=0.006) and LV-ESVI (102.2±24.9 to 42.5±9.9 ml/sqm, p=0.024), LVEF improvement (32% to 45%, p=0.016) and significant increase in CO and CI after surgical repair. Mitral repair/replacement was necessary in three patients. Postoperative reduction of mitral regurgitation (from grade 0.94 to 0.24, p=0.003) corresponded with improvement of MV geometry (CD (reduced from 10.2 to 7.9 mm, p=0.06) and of TA (1.8 to 1.5 sqcm, p=0.04) and MVCA (103° to 116°, p=0.04). Conclusions: Reconstruction of submitral LV aneurysms can be performed with good mid-term results. MSCT provides valuable information about aneurysm localization, its extent and effect on MV and LV geometry and reverse remodeling, and also functional changes after surgical restoration.
Abstract 18552: The Thrombin Inhibitor Dabigatran Inhibits High Fat Diet-induced Obesity and Fatty Liver Disease in Mice
Authors: Anna K Kopec, Karen M Kassel, Bradley P Sullivan, James P Luyendyk
Journal: Circulation (2012)

Inflammation associated with non-alcoholic fatty liver disease (NALFD) increases the risk of adverse cardiovascular events. NAFLD is the hepatic manifestation of obesity and the metabolic syndrome and significantly contributes to liver-related morbidity. We have shown previously that the thrombin receptor protease activated receptor-1 (PAR-1) is essential for hepatic inflammation and steatosis in mice fed a high fat diet (HFD), but PAR-1 deficiency does not affect weight gain in mice fed a HFD. To determine whether pharmacologic inhibitors of thrombin could reduce the progression of NAFLD in mice on a HFD, we utilized the direct thrombin inhibitor, dabigatran etexilate. Wild type C57Bl/6 mice were fed a HFD formulated to contain dabigatran (10 mg/g chow) or an identical HFD with starch substituted for drug for 3 months. Plasma thrombin time was significantly prolonged in mice fed HFD+dabigatran, but no adverse bleeding events were observed. Despite consuming a similar amount of chow, mice fed HFD+dabigatran gained significantly less body weight compared to mice fed HFD alone. Induction of inflammatory genes including TNFα, MCP-1, and the lipogenic genes SCD-1 and CD36, was significantly reduced in livers of mice fed HFD+dabigatran compared to mice fed HFD alone. In agreement, hepatic steatosis was dramatically reduced by dabigatran in mice fed a HFD. In summary, pharmacologic inhibition of thrombin with dabigatran reduced various features of NAFLD in mice fed a HFD. In contrast to PAR-1-deficient mice, dabigatran administration also dramatically reduced diet-induced obesity. Taken together, the results indicate that thrombin contributes to NAFLD in mice fed a HFD, and that thrombin promotes diet-induced obesity in a PAR-1-independent manner. Clinical evaluation of the potential for thrombin inhibition to reduce systemic and hepatic inflammation in obese patients taking dabigatran for another indication, such as atrial fibrillation, could reveal novel beneficial effects of oral thrombin inhibitors in metabolic disease.
Abstract 18467: Protective Effect of Nicotinamide Mononucleotide Administration Against Cardiac Ischemia/ Reperfusion Injury
Authors: Takanobu Yamamoto, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation (2012)

Background: Nicotinamide adenine dinucleotide (NAD) participates in metabolic reactions as an electron-transferring molecule. In the NAD biosynthetic salvage pathway, nicotinamide phosphoribosyltransferase (Nampt) which forms nicotinamide mononucleotide (NMN) is the rate-limiting enzyme and exhibits the protective effect against ischemia/ reperfusion (I/R) injury in the hearts of mice with cardiac-specific overexpression of Nampt. In addition, administration of NMN is reported to reverse the pancreatic beta-cell dysfunction observed in Nampt heterozygous knockout mice. Methods: To elucidate the protective effect of NMN against cardiac I/R injury, NMN was administered to mice subjected to I/R injury either before ischemia or immediately before reperfusion. Area at risk (AAR) and infarct area (IA) were evaluated 24 hours after reperfusion. Results: To confirm the distribution of NMN in the heart, NAD and NADH, into which NMN is quickly converted in the heart, were measured. One hour after NMN administration (500mg/ kg body weight, i.p.), the NAD and NADH contents of the NMN group were significantly increased, whereas the NAD/NADH ratio was unchanged compared to the vehicle group(NAD: NMN=483±42 pmol/mg tissue, vehicle=183±46 pmol/mg tissue, p&lt;0.01; NADH: NMN=262±25 pmol/mg tissue, vehicle=96±17 pmol/mg tissue, p&lt;0.01; NAD/NADH ratio: NMN=1.85±0.09, vehicle=1.82±0.18, n.s.; n=3). In the mice administered NMN or vehicle 30 min before ischemia, IA/AAR in the NMN group was smaller than that in the vehicle group (AAR: NMN=30±1.9%, vehicle=29±1.7%, n.s.; IA/AAR: NMN=23±2.9%, vehicle=41±2.6%, p&lt;0.01, n=6-7). On the other hand, in the mice administered NMN or vehicle immediately before reperfusion, IA/AAR in the NMN group was not different from that in the vehicle group (AAR: NMN=27±0.5%, vehicle=26±1.0%, n.s.; IA/AAR: NMN=37±1.4%, vehicle=34±2.2%, n.s., n=4). Conclusions: NMN administration significantly increased the NAD content in the heart and exhibited a protective effect against cardiac I/R injury. Increasing NAD content before ischemia, rather than after reperfusion, may minimize I/R injury in clinical settings, such as in acute coronary syndrome before coronary intervention.