tbuckley/cabot-search huggingface dataset:
Abstract 9337: Zofenopril is Cost Effective for Treatment of Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A Post- Hoc Analysis of the SMILE-4 Study
Authors: Claudio Borghi, Ettore Ambrosioni, Stefano Omboni, Arrigo F Cicero, Stefano Bacchelli, Daniela Degli Esposti, Salvatore Novo, Dragos Vinereanu, Giuseppe Ambrosio, Giorgio Reggiardo, Dario Zava
Journal: Circulation (2013)

Background and objective: in the Survival of Myocardial Infarction Long-term Evaluation 4 Study (SMILE-4) zofenopril associated with ASA was superior to ramipril plus ASA in reducing the occurrence of major cardiovascular events, in patients with left ventricular dysfunction (LVD) following acute myocardial infarction (AMI). The present post-hoc analysis was performed to evaluate cost-effectiveness of zofenopril compared to ramipril. Methods: a total of 771 patients with LVD and AMI were randomized double-blind to zofenopril 60 mg/day (n=389) or ramipril 10 mg/day (n=382) plus ASA 100 mg/day and followed-up for 1 year. The primary study end-point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on the evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n=716). Cost data were drawn from the National Health Service databases of the European countries participating into the study. The incremental cost-effectiveness ratio (ICER) was used to quantify the cost per event prevented with zofenopril vs. ramipril. Results: zofenopril significantly (p=0.028) reduced the risk of the primary study end-point by 30% as compared to ramipril (95% confidence interval: 49%, 4%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n=365) than with ramipril (165.12 Euros per patient per year, n=351). The cost related to the occurrence of major cardiovascular events requiring hospitalization, averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The ICER of zofenopril vs. ramipril was 2125.45 Euros per event prevented (worst- and best-case scenario in the sensitivity analysis: 3590.09 and 3243.96 Euros, respectively). Conclusions: zofenopril is a viable and cost-effective treatment for managing patients with LVD after AMI.
Abstract 14057: P Wave Indices and Atrial Fibrillation: Cross-Cohort Assessments from the Framingham Heart Study and Atherosclerosis Risk in Communities Study
Authors: Jared W. Magnani, Lei Zhu, Faye Lopez, Michael J. Pencina, Elsayed Z. Soliman, Emelia J. Benjamin, Alvaro Alonso
Journal: Circulation (2013)

Jared W. Magnani, 2013 Finalist and Presenting Author
Importance of Clinical Trials and International Cooperation
Authors: Marc A. Pfeffer
Journal: Circulation (2013)

As physicians, we are fundamentally biologists with the objective of utilizing this knowledge to limit disease burden. As medical practitioners and investigators, we strive to meaningfully contribute to this growing body of knowledge to improve the understanding of physiology and pathophysiology in an attempt to develop better therapeutic approaches for patients. Preliminary data from multiple sources are used to develop mechanistic constructs which can be focused into a testable hypothesis. In clinical investigation, the randomized controlled clinical trial (RCT) has emerged as the most definitive method of determining whether or not a novel therapy alters the clinical course of a cohort of patients with a defined disease. Although the skillful practice of medicine remains an art of using, at best incomplete data, the RCT provides the most quantitative assessments of both the benefits as well as the risks of a therapeutic strategy. However, RCTs that can provide such data are massive undertakings that require long-term dedication from large numbers of patients, investigators, and staff. As such, these large international cooperative ventures demand huge financial and personal commitments. As a consequence, smaller studies with more intermediate so-called surrogate outcomes are often conducted providing less definitive data that can only be extrapolated to presumed clinical outcomes. This presentation will highlight the advances and challenges of designing and conducting international clinical outcome trials with examples from cardiovascular medicine looking backwards as well as forward.
Abstract 10170: Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis from the JUPITER Trial
Authors: Amit V. Khera, Brendan M. Everett, Michael P. Caulfield, Feras M. Hantash, Jay Wohlgemuth, Paul M. Ridker, Samia Mora
Journal: Circulation (2013)

Amit V. Khera, 2013 Finalist and Presenting Author
Abstract 9648: Aldosterone Increases Transforming Growth Factor-β Expression to Activate Autophagy and Increase Aortic Fibroblast Collagen Synthesis and Vascular Stiffness
Authors: Samantha Torquato, Bradley A Maron, Joseph Loscalzo, Jane A Leopold
Journal: Circulation (2013)

Elevated levels of aldosterone (ALDO) are associated with aortic remodeling and increased arterial stiffness; however, the role of fibroblasts in these processes remains unknown. Accordingly, human aortic fibroblasts (HAoF) were treated with ALDO (10 -9 -10 -7 mol/L) or a vehicle control (V) for up to 72 h. Compared to V, ALDO increased HAoF expression of transforming growth factor-β (TGFβ) in a dose- and time-dependent manner with a maximal increase of 2.9 ± 0.3-fold (p&lt;0.01) at 72 h. This change was associated with a 252.6 ± 28.8 % (p&lt;0.01) increase in collagen III protein levels in ALDO-treated HAoF; these findings were confirmed by immunohistochemistry. Increased TGFβ expression was also associated with an increase in reactive oxygen species generation (126.4 ± 15.6 vs. 435.5 ± 38.6 fluorescent units, p&lt;0.01) and activation of autophagy as demonstrated by increased beclin1 expression (211.3 ± 23.2% vs. V, p&lt;0.01), lipidation of LC3BI to LC3BII (p&lt;0.01) and autophagic flux assay. To demonstrate that autophagy was necessary to increase collagen III expression, HAoF were transfected with beclin1 siRNA to decrease expression by 69%. Inhibition of autophagy led to a 78% decrease (p&lt;0.01) in collagen III expression without influencing TGFβ levels. To confirm these findings in vivo , C57Bl/6 mice received ALDO (50 μg/kg/d) or V for 21 days. In ALDO-treated mice, aortic TGFβ and LC3BII expression were increased with a concomitant 3.5 ± 0.5-fold (p&lt;0.01) increase in collagen deposition. Pulse wave velocity (PWV), a marker of arterial stiffness, was increased in ALDO-treated mice (288.4 ± 22.4 vs. 389.6 ± 19.8 cm/sec, p&lt;0.01). Treatment with imatinib (40 mg/kg/d) for 14 days downregulated vascular TGFβ expression, diminished collagen deposition, and decreased PWV by 41.1 ± 9.8% (p&lt;0.01). To determine the clinical relevance of these findings, human aorta segments from patients with atherosclerotic vascular disease had higher levels of TGFβ, LC3BII, and fibrosis compared to segments from subjects without disease. These data indicate that ALDO activates fibroblasts to modulate vascular collagen deposition and increase vascular stiffness through a mechanism that involves, in part, TGFβ-mediated activation of autophagy in fibroblasts.
Abstract 94: Performance of High-Sensitivity Cardiac Troponin T in Etiologic Diagnosis After Out-of-Hospital Cardiac Arrest
Authors: Guillaume Geri, Nicolas Mongardon, Florence Dumas, Camille Chenevier-Gobeaux, Olivier Varenne, Xavier Jouven, Benoit Vivien, Jean-Paul Mira, Jean-Philippe Empana, Christian Spaulding, Alain Cariou
Journal: Circulation (2013)

Purpose: Early identification of the cause of out-of-hospital cardiac arrest (OHCA) remains a challenge. Our aim was to determine whether high-sensitivity cardiac troponin T (HsTnT) was useful to diagnose a recent coronary artery occlusion as the cause of OHCA. Methods: Retrospective study including OHCA patients evaluated by systematic coronary angiogram at hospital admission. HsTnT was assessed at ICU admission. Predictive factors of a recent coronary occlusion were identified by logistic regression. Net reclassification improvement (NRI) was calculated to estimate the potential enhancement of prediction with HsTnT. Results: During the 5 years study period, 272 patients (median age 60y, 76.5% men) were included, and a culprit coronary occlusion was found in 133 (48.9%). Median HsTnT at admission was 551 (IQR 203-2551) ng/l, up to three times higher in patients with compared to those without a recent coronary occlusion (1184 vs. 351 ng/l; p&lt;0.0001). The optimum HsTnT cut-off to predict a recent coronary occlusion was 575 ng/l (sensitivity 65.4%, specificity 65.5%). In multivariate analysis, current smoking (OR 3.2 95%, 95%CI 1.62-6.33), time from collapse to BLS &lt; 3 minutes (OR 2.11, 95%CI 1.10-4.05), initial shockable rhythm (OR 5.29, 95%CI 2.06-13.62), ST-segment elevation (OR 2.44, 95%CI 1.18-5.03), post-resuscitation shock onset (OR 2.03, 95%CI 1.01-4.07) and HsTnT ≥ 575ng/l (OR 2.22, 95% CI 1.16-4.27) were associated with the presence of a recent coronary occlusion. The AUROC curves of the multivariate model identified above were not statistically better than those of the same model with established risk factors but without HsTnT (AUROC curves= 0.78 vs. 0.79; p=0.23). Nevertheless, adding HsTnT to established risk factors of recent coronary occlusion identified above provided a non-significant NRI of -0.43%. Reclassification was not better in the subgroup of patients without ST-segment elevation (NRI= 0.105±0.078, p=0.18). Conclusions: Admission HsTnT is increased after OHCA and is an independent factor of a recent coronary occlusion. However, HsTnT does not seem to be a strong enough diagnostic tool to select candidates for emergent coronary angiogram in OHCA survivors.
Abstract 9432: Superior Long-term Prognostic Impact of Angiotensin Converting Enzyme Inhibitors to Angiotensin II Receptor Blockers After ST-Elevation Myocardial Infarction
Authors: Masahiko Hara, Yasuhiko Sakata, Daisaku Nakatani, Shinichiro Suna, Masaya Usami, Sen Matsumoto, Toshifumi Sugitani, Masami Nishino, Hiroshi Sato, Tetsuhisa Kitamura, Shinsuke Nanto, Toshimitsu Hamasaki, Masatsugu Hori, Issei Komuro
Journal: Circulation (2013)

Masahiko Hara, 2013 Finalist and Presenting Author
Abstract 9883: Impact of Low Transvalvular Gradient on Early and Late Outcomes After Aortic Valve Replacement for Aortic Stenosis
Authors: Kenji Kuwaki, Atsushi Amano, Hirotaka Inaba, Taira Yamamoto, Terumasa Morita, Shizuyuki Dohi, Akie Shimada, Kishio Kuroda
Journal: Circulation (2013)

Background: Few data are available concerning the results of aortic valve replacement (AVR) for low-gradient severe aortic stenosis (AS). Aim of this study was to assess the hypothesis that low-gradient is an independent predictor of early and late results after AVR. Methods: We retrospectively analyzed a series of 340 consecutive AS patients (area≦1.0cm 2 ) who underwent AVR from 2002 to 2012. Low-gradient AS was defined by the mean transvalvular gradient &lt;40mmHg (n=68, 20%). The outcome measures included hospital mortality, major postoperative complication, prolonged length of hospital stay, and late survival. Results: Hospital mortality was 3.2% (n=11) (low-gradient 8.8%; high-gradient 1.8%; p=0.01). Low-gradient AS was an independent predictor for hospital mortality (odds ratio [OR] 6.0, 95% confidence interval [CI]: 1.6 to 21.2, p=0.006), but did not predict any postoperative major complication. NYHA class III/IV was another independent predictor of hospital mortality (OR 19.3, 95%CI: 2.4 to 155.1, p=0.005). In the patients with low-gradient AS who were in NYHA class III/IV (n=25), hospital mortality was significantly higher (24%) compared to those in NYHA class II (n=43, hospital mortality 0%). Multivariable predictors of late mortality (excluding hospital death) included NYHA class III/IV (OR 9.6, 95%CI: 1.2 to 76.7, p=0.03) and creatinine &gt;2mg/dl (OR 6.9, 95%CI: 2.1 to 22.8, p=0.002). Low-gradient was no longer a risk of late mortality in operative survivors. The survival rate at 7 years after AVR was 84±10% in low-gradient and 95±2% in high-gradient patients (p=0.42). We also calculated propensity score for low-gradient status (C-statistic: 0.71), and 37 low-gradient were matched to 41 high-gradient patients. No statistically significance was observed in late survival between propensity matched low and high-gradient patients (83% vs 95% at 7 years, p=0.86). Conclusions: Low-gradient AS was an independent predictor of increased hospital mortality, but did not predict late mortality in operative survivors. Surgical risk was very high in low-gradient patients with advanced NYHA class. However, AVR could be performed safely if low-gradient AS patients were in NYHA class II, and good long-term survival was seen in operative survivors.
Abstract 19052: Readmissions After Implantation of Continuous-Flow Left Ventricular Assist Devices: A Comparison Between the HeartMate II and the HeartWare Devices
Authors: Nicholas A Haglund, Mary E Davis, Anna H Gallion, Rashid A Ahmad, Thomas J DiSalvo, Mary E Keebler, Daniel J Lenihan, Kelly H Schlendorf, Mark A Wigger, Simon Maltais
Journal: Circulation (2013)

Background: Readmissions after implantation of continuous-flow left ventricular assist devices (CF-LVAD) are common. The ADVANCE Trial fails to compare readmissions between the HeartMate II (HMII) LVAD and the HeartWare VAD (HVAD). We sought to compare the frequency and causes of early (60 day) readmissions after implantation of these two devices. Methods: We retrospectively evaluated readmissions at Vanderbilt University Medical Center in a cohort of 65 patients implanted between April 2009 and April 2013 with the HM II LVAD (n= 46) and the HVAD (n=19). All hospitalizations between time of LVAD implant and 60 days were analyzed. Results: Preoperative patient characteristics (age, LVEF, % reoperation, % ischemic etiology), and preoperative risk stratification (INTERMACS category, Leitz-Miller score, Kormos score) were comparable between groups (all p&gt;0.05). There were 37 readmissions for 28 patients within the first 60 days after device implant. Twenty-six readmissions (70%) occurred between 0-30 days, 11 (30%) between 30-60 days. Overall, the most common reasons for readmission within the first 60 days of implant were Cardiac (heart failure (7) and arrhythmia (6)) n= 13 (35%), other (dehydration (6), pain (1), VAD disconnect (1), elevated INR (2)) n=10 (27%), infection (driveline (2), non-driveline (4)) n=6 (16%), thrombosis (pump (3), hemolysis (1), stroke (1)) n=5 (14%), and bleeding (gastrointestinal (2), hemorrhagic stroke (1)) n= 3 (8%). Readmission frequency in patients with a HMII versus HVAD device type (27 readmissions in 22 patients with HMII vs 10 admissions in 7 patients with HVAD) was not different p=0.40. Conclusion: Readmission rate after CF-LVAD implantation is frequent (45%) especially within the first 30 days. There are no differences in readmission rate among CF-LVAD types. Understanding these causes is critical for clinical management and institutional efforts to reduce CF-LVAD readmission rates and associated costs.
Abstract 9460: Increased Aortic and Main Pulmonary Arterial Diameters Are Independent Predictors of Incident Cardiovascular Disease Events
Authors: Michael L Chuang, Philimon Gona, Carol J Salton, Connie W Tsao, Susan B Yeon, Warren J Manning, Christopher J O’Donnell
Journal: Circulation (2013)

Introduction: Aortic dilation is associated with multiple cardiovascular disease (CVD) risk factors. We sought to determine whether enlargement of the aorta or main pulmonary artery (MPA) is an independent predictor of future adverse CVD events. Methods: 1715 Framingham Offspring cohort members without prevalent CVD (69±9 y, 47% men) underwent cardiovascular magnetic resonance (CMR) of the aorta and MPA during 2002-2005. CMR at 1.5T used a free-breathing, ECG gated, black blood, fat suppressed T2-W turbo spin-echo sequence with 1.03x0.64-mm2 spatial resolution and 5-mm slice thickness. Luminal diameters of the ascending (ASC) and descending thoracic (DTA) aorta and MPA were measured at the level of MPA bifurcation, the abdominal aorta (ABD) was measured just below the renal arteries. Incident hard CVD events included CV death, myocardial infarction, coronary insufficiency, stroke and hospitalized congestive heart failure. For each vessel segment Cox proportional hazards regression models (adjusted for age, sex, body mass index, systolic blood pressure, pack years smoked; treatment for hypertension, diabetes or dyslipidemia; current smoking; emphysema) were used to assess hazard of a hard CVD event per 5mm of vessel diameter. Results: Over a mean 6.5-year follow up there were 60 (3.3%) incident hard CVD events. The Table shows mean±SD diameters by sex and sex-pooled hazard ratios (HR) and 95% confidence intervals (CI) for hard CVD events per 5 mm increase in vessel diameter. Men had greater mean diameters than women. Increasing diameter of each vessel segment, except ASC, was associated with greater multi-variable adjusted hazard of adverse CVD events. Results were qualitatively similar after indexation of diameters to height. Conclusion: In a community-dwelling cohort of adults initially free of clinical CVD, greater luminal diameter of the descending aorta or the MPA, measured by noncontrast CMR, is an independent predictor of future adverse CVD events.
Abstract 19074: Multi-Vessel Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells in a Porcine Model of Myocardial Infarction
Authors: Eleni Tseliou, Hideaki Kanazawa, James Dawkins, Supurna Chowdhury, Ryan Middleton, Rachel Smith, Michelle Kreke, Linda Marbán, Raj Makkar, Eduardo Marbán
Journal: Circulation (2013)

Background: Single-vessel, intracoronary cardiosphere derived cells (CDCs) have been shown to be safe and effective in both preclinical and clinical studies. However, the potential utility of multivessel intracoronary delivery to target global left ventricular remodeling post-myocardial infarction (MI) has not been studied. Objective: We sought to evaluate the safety and efficacy of multivessel intracoronary delivery of allogeneic CDCs in a porcine model of subacute MI. Methods: MI was created in adult female Yucatan minipigs. Three weeks later, 12.5M allogeneic CDCs were infused sequentially in each of the three coronary vessels; LAD, LCX and RCA under stop-flow (Group 1) or nonocclusive-flow conditions (Group 2). Animals infused with vehicle under stop flow conditions served as the control group (Group 3; n=5 per group). Animals underwent MR imaging at baseline (just before infusion) and 4 weeks post-infusions. Left ventricular ejection fraction, scar mass and viable mass were evaluated at both time points. Results: Ejection fraction (EF) did not differ among the three groups at baseline. However, LV function was better preserved in both CDC infusion groups compared to vehicle at 1 month follow-up (ΔEF=-4+/-1.6% in Group 1, p=0.13; ΔEF =-1.1+/-2.2% in Group 2, p=0.7; ΔEF=-4.6+/-2.3% in Group 3, p=0.05). In terms of scar mass, CDCs under both stop-flow and non-occlusive infusion technique reduced 1 month post-treatment compared to the vehicle group (Δscar mass= -2.9+/-0.6gr in Group 1, p=0.012; Δscar mass= -1.2+/- 0.4gr in Group 2, p=0.028; Δscar mass =-1.9+/-1.1gr in Group 3, p=0.16). Viable mass was not changed significantly in any of the groups (p=ns). No humoral response (by circulating antibodies) or additional cell inflammatory response (by histopathological analysis) were detected 1 month post infusion in the continuous flow CDCs group. Serum troponin I measured at 24 hrs was routinely elevated in the stop-flow group, but not in the nonocclusive flow group. Conclusions: Nonocclusive multivessel delivery of allogeneic CDCs is safe and effective to preserve left ventricular function as soon as 1 month post-delivery, paving the way for future applications targeting global left ventricular remodeling.
Abstract 9950: Immunoadsorption can Improve Cardiac Function in Transplant Candidates With Non-Ischemic Cardiomyopathy Associated With Diabetes Mellitus
Authors: Michael Dandel, Angela Englert, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2013)

Background: Diabetes mellitus (DM) is a risk factor for death by heart failure (HF). With prolongation of waiting times for heart transplantatation (HTx) new therapies are necessary to improve survival. Diabetic patients are also less eligible for HTx and DM is a risk factor for death also after HTx. In dilated cardiomyopathy, immunoadsorption (IA) can improve heart function and delay HTx listing, but its usefulness for therapy of HF associated with DM is unknown. We assessed this aspect. Methods: Cardiac function and freedom from HF recurrence were evaluated in HTx candidates with non-ischemic chronic cardiomyopathy (NICCM) associated with DM who underwent IA in 6/2003-6/2012 (follow up 1–10 yrs). Non-diabetic NICCM patients referred for HTx in the same time period and who received the same IA served as controls. Before and after IA patients were tested for serum β 1 -autoantibodies (β 1 -AABs). Results: We evaluated 64 HF patients (32 with and 32 without DM). Before IA there were no differences between the 2 groups, neither in LV size and EF, nor in brain natriuretic peptide or β 1 -AAB levels. However, diabetic patients were older (51.5 ±7.0 vs. 44.2 ±12 yrs; p=0.005), their HF duration was longer (6.8 ±5 vs. 3.6 ±3 yrs; p&lt;0.001) and their peak oxygen-uptake was lower (p=0.004). During the 1 st post-IA year in both groups there a decrease in LV size and improvement in both LVEF (from 26.4±7 to 31.3±7% and from 25.6±6 to 31.2±9%, respectively) and NYHA class (p&lt;0.05 for all). Post-IA 3-year freedom from HF recurrence and prevalence of responders to IA in patients with and without DM reached 81.3±8% and 78.4±8%, respectively and 73.3% and 67.7%, respectively. Post-IA 3-year freedom from β 1 -AAB reappearance in patients with and without DM reached 72.1±9.0% and 71.1±8.6%, respectively. Conclusions: IA improves heart function and exercise tolerance in patients with end-stage NICCM, with and without additional DM. Responsiveness to IA and freedom from HF recurrence where similar in patients with and without DM, although DM patients were older and had longer duration of HF. IA appeared able to delay HTx listing, improve survival on HTx lists and even spare patients from HTx, benefits of particular importance for DM patients who are at higher risk for pre-HTx and post-HTx mortality.