tbuckley/cabot-search huggingface dataset:
Abstract 9436: Impact of Aortic Valve Calcification Severity and Impaired Left Ventricular Function on Long-Term Outcome After Transcatheter Aortic Valve Replacement: 24 Months Results From the Aachen Registry
Authors: Ralf Koos, Sebastian Reinartz, Shahram Lotfi, Rüdiger Autschbach, Nikolaus Marx, Rainer Hoffmann
Journal: Circulation (2013)

Introduction: Transcatheter aortic valve replacement (TAVI) has been established in high-risk patients with severe aortic valve stenosis. We aimed to evaluate pre-interventional clinical predictors of two-year outcome and mortality in a real-world population treated with TAVI. Methods: Consecutive patients with symptomatic aortic valve stenosis (aortic valve area ≤ 1cm 2 ) undergoing TAVI were prospectively included into the Aachen TAVI registry. Among 346 patients, 105 patients (34 men, mean age 81 ± 6 years, logistic EuroSCORE of 21 ± 12) with a baseline dual-source computed tomography (DSCT) and a two-year follow-up were identified. Prior to TAVI, all patients received an echocardiography and underwent a non-enhanced and contrast-enhanced DSCT (Definition, Siemens, Forchheim, Germany with scan parameters as follows: 2x64x0,6mm collimation, tube voltage 120KV, 380mAs tube current) for quantification of aortic valve calcification (AVC) severity using the Agatston AVC score. Mortality tracking was achieved in 100% of patients. Results: Survival at 30 days was 90 %, and it was 63% at 2 years. NYHA class showed a marked improvement from 3.2 ± 0.6 at baseline to 1.4 ± 0.6 at 2 years. Non-survivors at 2 years showed a significantly higher Agatston AVC score (2722 ± 1485) than survivors (1809 ± 997, p=0.001). Multivariate analysis including age, logistic EuroScore, glomerular filtration rate, Agatston AVC score, ejection fraction &lt; 40% and NYHA class revealed that only the Agatston AVC score (p&lt;0.001) and impaired left ventricular function (p=0.021) was significantly associated with mortality. Patients with Agatston AVC scores &gt; 1900 (above the median of the total cohort) had a significantly lower 2-year survival rate compared to patients with scores &lt; 1900 (47% vs. 78%, p=0.001). Conclusions: In patients referred for TAVI, aortic valve calcification severity and impaired left ventricular function may serve as a predictor of long-term mortality. Therefore, aortic valve calcification scores easily to be determined from preprocedural CT-datasets may be used for patient risk stratification.
Abstract 280: Prehospital ECLS for Refractory Cardiac Arrest: Safety and Feasibility Study
Authors: Lionel Lamhaut, Romain Jouffroy, Christelle Dagron, Thibaut Deluze, Pascal Phillipe, Marc Lejay, Kim An, Christian Spalding, Pierre Carli
Journal: Circulation (2013)

Background: Extra Corporeal Life Support (ECLS) has been introduced in the treatment of refractory cardiac arrest (RCA). Several studies have assessed the use of ECLS in RCA once the patient has reached the hospital. The time between RCA and implementation of ECLS (low flow time) is one of the succesfull prognostic factors for survival. Pre hospital ECLS(PH-ECLS) implementation could decrease access time. Hence, we decided to assess the feasibility and safety of PH-ECLS implementation in a pilot study to reduce the low flow time. Methodology: We have developed a PH-ECLS team. This team was composed by 2 emergency physicians, 1 nurse, 1 paramedic. Patients were included prospectively and consecutively if the following criteria were gathered: they had a witnessed CA; CPR was initiated within the first 5 minutes and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. According to national guideline, RCA was defined failed after 30 minutes of ALS. The ECLS insertion started after this 30 minutes of ACLS. The insertion technics was a surgical opening of the scarpa to repair the vessel. The insertion was done by Seldinger technics. Results: From 10/2011 to 01/2013, 17 patients with out of hospital CA were included. Results are resumed in Table 1. Discussion: This study shows the safety and feasibility to insert ECLS for OHCA on scene by emergency physician. The success rate and the insertion time are similar compare to the same technic in hospital by surgeon. One of the failed insertions was due to the obesity of the patient. Within this sample, one patient survived without sequel. However this study was not designed for survival, only for the safety and feasibility. One of the limitations in this work was the delay to define a RCA. The defined time of 30 minutes of ALS was too long to hope survivor regarding to the literature. PH-ECLS can be a solution to reduce the low flow time but a randomized study is required to evaluate the effect on survivors.
Abstract 9562: Liver Dysfunction Assessed by Model of End-stage Liver Disease Excluding INR (MELD-XI) Scoring System Predicts Adverse Prognosis in Heart Failure
Authors: Takeshi Shimizu, Akiomi Yoshihsa, Mai Takiguchi, Hiroyuki Yamauchi, Takashi Owada, Shoji Iwaya, Makiko Miyata, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2013)

Background: Liver dysfunction due to end-stage heart failure (HF) is often referred as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in heart transplant recipients. However, the impact of MELD-XI scores on cardiac function and prognosis in general HF patients still remains unclear. Methods and Results: We retrospectively analyzed 550 patients with HF who admitted to our hospital. Liver function was estimated by MELD-XI formula (5.11хlog (bilirubin)+ 11.76хlog (creatinine)+9.44). These patients were divided into two groups based on the median MELD-XI score: Group L (MELD-XI &lt;10, n=269) and Group H (MELD-XI ≥10, n=281). We compared echocardiographic findings and cardiac event rates including cardiac deaths and re-hospitalization due to worsening HF between two groups. In echocardiographic paremeters, left atrial volume (LAV), right atrial area (RAA), right ventricular diastolic area (RVAd), right ventricular systolic area (RVAs), inferior vena cava diameter (IVC) were higher, and left ventricular ejection fraction (LVEF) was lower in group H than in group L (LAV: 93.7 vs. 74.0 ml, RAA: 25.0 vs. 16.5 cm 2 , RVAd: 17.1 vs. 15.7 cm 2 , RVAs: 10.6 vs. 9.1 cm 2 , IVC: 15.9 vs. 14.4 mm, LVEF: 45.5 vs. 50.4%, P&lt;0.05, respectively). Right ventricular fractional area change did not differ between 2 groups. In addition, 151 events (52 deaths and 99 re-hospitalizations) occurred during the follow-up period (mean 348 days). Importantly, the event-free rate was significantly higher in group L than in group H (78.4% vs. 66.9%, logrank P =0.001). In the Cox proportional hazard analysis, higher MELD-XI (MELD-XI ≥10) was an independent predictor of cardiac events in HF patients (hazard ratio 1.79, 95% confidence interval 1.29-2.49, P=0.001). Conclusions: A MELD-XI scoring system, a marker of liver function, can identify high risk patients associated with larger right heart volume overload, left ventricular systolic dysfunction, and adverse clinical outcomes in HF.
Abstract 9519: Knockdown of TRPC1 Expression Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model: Advantage of Liposome-Mediated siRNA Delivery System
Authors: Tzu -Hsien Tsai, Sarah Chua, Jiunn-Jye Sheu, Hon-Kan Yip
Journal: Circulation (2013)

Background: We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC)1 protein expression can suppresses hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Methods and Results: Adult male C57BL/6 mice (n=30) were equally divided into group 1 (normal controls), group 2 (hypoxia for 28 days), group 3 [hypoxia + Lipofetamine-delivered siRNA to knockdown TRPC1 (intra-tracheally administered on day 14 after hypoxia)]. By day 28, right ventricular blood pressure (RVSBP), number of muscularized arteries, RV and the lung weight were increased in group 2 than in group 1, and reduced in group 3 compared with group 2 (all p&lt;0.001). Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSBP in the three groups (all p&lt;0.0001). Protein expressions of TRPCs (1, 4, 6), HIF-1α, Ku-70, apoptosis (Bax, cleaved caspase 3, and PARP) and fibrosis (Smad3, TGF-β) and pulmonary mRNA expressions of inflammatory markers (MMP-9, TNF-α) was similar to, whereas protein expressions of anti-fibrosis (Smad1/5, BMP-2) and VEGF was opposite to the pattern of RVSBP (all p&lt;0.01). Cellular markers of pulmonary DNA damage (γHA2X), repair (Ku-70), and smooth-muscle proliferation (Ki67) exhibited a pattern similar to that of RVSBP (all p&lt;0.001). Pro-apoptotic mRNA expressions of (Bax, caspase 3) and hypertrophy (β-MHC) displayed a similar pattern, whereas sacromere length showed an opposite pattern compared to that of RVSBP in all groups (all p&lt;0.001). Conclusion: Lipofectamine siRNA delivery effectively knockdown PRTC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.
Abstract 9781: Cost-Effectiveness of Same-Day Discharge After Elective Percutaneous Coronary Intervention
Authors: Kimberly Brayton, Sze-chuan Suen, Vishal G Patel, Douglas K Owens, Jeremy D Goldhaber-Fiebert
Journal: Circulation (2013)

Objective: Same-day discharge (SDD) appears to be safe in highly selected patients undergoing PCI, however the economic impact of SDD compared to overnight observation has not been comprehensively assessed. Methods: We developed a decision-analytic Markov model to compare SDD to overnight observation post-PCI (Figure). Patients were followed from index PCI over remaining lifetime, including the possibility of future revascularizations. Inputs were derived from registries, RCTs, and meta-analyses. We adjusted mortality rates for having had a prior adverse procedural outcome. Costs were estimated using micro-costing (2012 USD), and outcomes were measured in QALYs, both considered from a societal perspective and discounted at 3% annually. Results: Base case analysis demonstrated that SDD cost $1,639 less but delivered 0.0028 fewer QALYs ($585,000 saved per QALY lost) compared to overnight observation. This result was sensitive to adverse outcome probabilities. SDD cost less and provided more QALYs when the probabilities of adverse outcomes for SDD were lower (&lt;0.57% death, &lt;0.60% major bleeding, or &lt;2.32% MI) or when the probabilities of adverse outcomes for overnight observation were higher (&gt;0.63% death, &gt;0.90% major bleeding, or &gt;2.89% MI). However, SDD cost more and was less effective if rates of SDD adverse events were substantially higher (&gt;6.46% for MI) but still within the 95% confidence interval. Probabilistic sensitivity analyses revealed that SDD was frequently cost-effective even at high willingness-to-pay thresholds. Conclusion: SDD appears to be cost-effective if its safety profile is confirmed to be nearly identical to overnight observation. The attractiveness of SDD may depend on the ability of health systems to re-allocate resources to achieve anticipated cost savings, and to monitor and respond to adverse events out of the hospital.
Abstract 9684: Favourable Midterm Outcome After Heart Transplantation for Late Fontan Failure
Authors: Guido Michielon
Journal: Circulation (2013)

Background: Fontan failure (FF) represents a growing and challenging indication for pediatric orthotopic heart transplantation (OHT).The aim of this study was to identify predictors of best midterm outcome in OHT after FF. Methods: retrospective multi-institutional study on 45 consecutive patients who underwent OHT for FF between 1992 ans 2011. Mean follow-up was 72.8±70.5 month and was 100% complete. Early FF was defined as failure requiring OHT within 2 years from Fontan completion. Results: 45 patients underwent OHT 8.6±6.1 years after Fontan completion due to failing atriopulmonary (12) or TCPC (33). Modality of FF included protein losing enteropathy (PLE) (31%), complex obstructions in Fontan circuit (22%), arrhythmia (18%) and impaired ventricular function (29%). Early FF occurred in 15.6% patients. Mean age at OHT was 12.4±4.9 years. Hospital mortality was 17.8% and late mortality was 13.5%. Main causes of early death were infection (37.5%) and graft failure (37.5%). Mean time of mechanical ventilation was 8.6±2.3 days while mean hospital stay was 40.1±7.2 days. Overall Kaplan Meier (KM) survival was 82.2±5.7% at 1 year, 78.4±7.0% at 5 years and 55.3±11.2% at 10 years. KM one-year OHT survival was 89.5±5.1% in late FF and 42.9±9.7% in early FF (p=0.0031). Fisher exact testing showed a strong correlation between late FF and impaired ventricular function (p=0.0226). OHT survival for late FF was 84.5±6.7% at 5 years and 59.7±13.0% at 10 yrs. Protein dispersion improved after OHT in 78.6% patients with PLE, but overall 5-year OHT survival in PLE was 45.9±12.1 versus 87.1± 6.0% in non-PLE (p=0.027). Early FF (p=0.0017), PLE (p=0.0157) and complex obstructions of Fontan circuit (p=0.0087) were identified as independent predictors of mortality by Cox proportional hazards. Conclusions: OHT is an excellent surgical option for late FF with impaired ventricular function. Protein dispersion improves with OHT, but PLE and complex obstructions of Fontan circuit negatively affect midterm OHT outcome.
Abstract 9843: Proton Pump Inhibitors Inhibit DDAH and Processes Underlying Idiopathic Pulmonary Fibrosis
Authors: Yohannes T Ghebremariam, Lawrence Ho, Glenn D Rosen, John P Cooke
Journal: Circulation (2013)

Rationale: The cardiovascular enzyme dimethylarginine dimethylaminohydrolase (DDAH) has recently been implicated in the progression of idiopathic pulmonary fibrosis (IPF). By degrading asymmetric dimethylarginine (ADMA), an inhibitor of inducible nitric oxide (NO) synthase (iNOS), DDAH releases the brake on a pathway implicated in lung injury and fibrosis. In addition, DDAH promotes the pro-fibrotic activity of the TGFβ pathway. Objectives: We embarked on studies to discover DDAH inhibitors, and to assess the effect of such inhibitors on processes involved in IPF. Methods: We performed high throughput screening (HTS) of over 130,000 small molecules and discovered that the proton pump inhibitors (PPIs) modestly inhibit DDAH. We used cellular and molecular assays to study the effect of the PPIs on DDAH activity by measuring the concentration of ADMA. In addition, we assessed the effect of PPIs on collagen synthesis by IPF lung fibroblasts, and on the survival and proliferation of lung alveolar epithelial cells. Finally, a retrospective analysis of the Stanford University interstitial lung disease (ILD) database was performed to assess the effect of PPIs on transplant-free survival. Results: We found that the PPIs inhibit DDAH activity in biochemical assays, cell culture and in vivo. The resulting increase in ADMA level was mirrored by a reduction in NO production. In addition, the PPIs reduced the production of soluble collagen by primary IPF lung fibroblasts in response to TGFβ and regulated both proliferation and survival of lung alveolar epithelial cells. Retrospective review of the ILD database of 131 IPF patients (of who 85 were on PPIs for &gt; 1 year) revealed a survival advantage (i.e. time to transplant or death when calculated from the time of diagnosis) of the patients on PPIs, including those without symptoms of Gastroesophageal disease (GERD); an indication for which the PPIs are primarily prescribed for, suggesting the involvement of a mechanism other than acid-suppression. Conclusions: Our data reveal a plausible biological explanation for the clinical benefit of the PPIs in IPF. The reported reduction in radiologic fibrosis score and significant survival advantage of IPF patients on PPIs may be due to modulation of the DDAH/NOS pathway.
Abstract 9452: Comparative Study of Adipose Derived Regenerative Cells versus Bone Marrow-Mononuclear Cells for Therapeutic Angiogenesis
Authors: Chang-ning Hao, Satoshi Shintani, Yuuki Shimizu, Hong-xian Wu, Kazuhisa Kondo, Masakazu Ishii, Toyoaki Murohara
Journal: Circulation (2013)

Objective: Due to the poor prognosis of therapeutic angiogenesis by bone marrow-mononuclear cells (BM-MNCs) to severe atherosclerotic patients, we focused on adipose-derived regenerative cells (ADRCs) as an alternative choice. Here, we compared the therapeutic efficacy between these two cells in two animal models of hindlimb ischemia (HLI) and further tested the hypothesis that ADRC augments angiogenesis by regulating local hemostasis through macrophage polarization. Methods and Results: We observed that fluorescence labeled ADRCs incorporated into vasculature in vitro and vivo. Then, we compared the paracrine manner between ADRCs and BM-MNCs using conditioned media (CM). Accelerated migratory ability and prevented apoptosis of human umbilical vein endothelial cells (HUVECs) were observed treated by both CM compared with control. In vivo study, implantation of either ADRCs or BM-MNCs revealed more angiographically detectable collateral vessels formation, higher capillary density, greater cuff blood pressure ratio, and stronger laser Doppler blood perfusion signals than control in rabbit HLI model. In mice study, we proved ADRCs changed the polarity of infiltrated macrophage into M2 phenotype through prostaglandin E2 (PGE2) and EP2/4 receptors. Next, the mRNA expression of several angiogenic cytokines were up-regulated in the macrophages cultured in ADRC-CM compared with BM-MNC-CM. ADRCs implantation also muted local inflammation and apoptosis via down-regulating the gene expression of pro-inflammatory cytokines, as well as increasing interleukin (IL)-10. Finally, blockade of IL-10 by neutralizing monoclonal antibody resulted in harsher microenvironment and attenuated ischemic-induced angiogenesis in mouse HLI model. Conclusions: In conclusion, the safety and efficacy of therapeutic angiogenesis by ADRCs implantation was comparable with BM-MNCs in rabbit HLI model. Moreover, slanted M2 polarity of infiltrated macrophages was observed after ADRCs implantation through PGE2 - EP2/4 - IL-10 axis, leading to facilitation of postnatal neovascularization via their angiogenic, anti-inflammatory and anti-apoptotic manners.
Abstract 7: Myocardial Electrical Remodeling and Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart
Authors: Bonpei Takase, Yoshihiro Tanaka
Journal: Circulation (2013)

Rationale: Lethal arrhythmias such as ventricular tachycardia and ventricular fibrillation (VT/VF) is one of the most serious complications after the resuscitation of severe hemorrhagic shock, even though systemic hemodynamics seems to recover. Objectives: To investigate the mechanisms of arrhythmogenesis after hemorrhagic shock and a role of oxygenated hemoglobin transfusion, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examination were performed using an acute hemorrhagic shock model of rats. Measurement and Main Results: After cannulating 22G catheter into the lower abdominal aorta, rats were subjected to acute hemorrhagic shock by withdrawing 30% of total blood volume (TBV) for 25 min, and observed for 15 min (shock alone). After acute hemorrhagic shock, the rats were immediately resuscitated by transfusing exactly the same amount of saline, 5% albumin (5%ALB), oxygenated liposome-encapsulated human hemoglobin (LHb), or oxygenated autologous washed red blood cells (wRBC) (n = 7, per group). After excising the heart, OMP and EPS were performed in isolated Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in both ventricles in shock alone, saline, and 5%ALB. In contrast, myocardial conduction velocity and APD dispersion in both ventricles were substantially attenuated in LHb or wRBC. VT/VF spontaneously occurred in shock alone. Furthermore, sustained VT/VF was easily provoked by burst pacing stimulus to the LV in saline and 5%ALB. No VT/VF was induced in the LV when the heart was resuscitated with oxygenated LHb or wRBC. Pathology including electron microscopy and immunohistochemistry demonstrated myocardial structural damages characterized by degradation of sarcometric actin and connexin43 in shock, saline, and 5%ALB. However, these histological changes were substantially attenuated in LHb and wRBC. Conclusion: Ventricular structural remodeling after hemorrhagic shock causes VT/VF only in the presence with APD dispersion. Oxygenated hemoglobin transfusion prevents VT/VF by preserving myocardial structures caused by ischemia-reperfusion injury in hemorrhagic shock.
Abstract 9632: Mitral Regurgitation and Atrial Fibrillation: Is it Worth Cardioverting?
Authors: Mohammed Qintar, Muhammad Hammadah, James Thomas, Mina Chung
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) presents in 30%-40% of patients presenting for mitral regurgitation (MR) surgery but may contribute to functional MR. Although severe MR often inhibits consideration of cardioversion (CV), restoring sinus rhythm (SR) or rate control might yield benefits. We tested the hypothesis that in patients with 3-4+MR, restoring and maintaining SR after CV can significantly improve MR to non-surgical ranges (≤2+MR). Methods: From a prospectively collected database of CV procedures, we retrospectively identified patients undergoing their first CV with an echo within 1 year showing moderately severe to severe 3-4+MR and with a follow-up echo within 1 year after CV. Their CV had to be successful. Of 9333 patients undergoing first CVs, 433 met inclusion criteria. Patients with intervening valve surgery were excluded. The primary outcome was reduction in MR to ≤2+. Paired t-tests were used to analyze changes in MR, LVEF, and TV. Echocardiographic and clinical predictors of improvement were determined using multivariate regression models. Results: Paired t-tests showed improvement in MR irrespective of rhythm during follow up, although greater improvement was observed in patients with SR vs AF at follow up (mean pair change (MPC) 0.83 ± 1.05, 95% CI 0.616-1.054, p&lt;0.001 vs 0.47 ± 0.90, 95% CI 0.212-0.727, p=0.001, respectively). 55% of patients with 3-4+MR had no more than moderate (2+) residual MR at follow-up if they maintained sinus rhythm compared to 38% in patients with recurrence of atrial fibrillation (Figure, p=0.033). LVEF and TR also improved with maintenance of sinus rhythm (Figure). Conclusion: Despite moderately severe to severe MR at baseline, clinically significant improvement in MR was observed after successful CV, especially with maintenance of sinus rhythm at follow up.