Publications by authors named "Imtiaz Ali"

55 Publications

Clinical and hemodynamic outcomes of the Dor procedure in adults with ischemic cardiomyopathy.

J Card Surg 2021 Sep 7. Epub 2021 Sep 7.

Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Ischemic cardiomyopathy continues to be a major contributor to congestive heart failure, which places a significant burden on our healthcare system. Improving medications and different coronary revascularization strategies are the mainstays in the management of ischemic cardiomyopathy. Although medications and mechanical circulatory support are playing an ever-increasing role, cardiac transplantation remains the gold standard for treating advanced heart failure. Given the small number of available and suitable donor hearts, transplantation is limited for the majority of patients. Surgical ventricular restoration has repeatedly been suggested as a viable alternative in managing heart failure in select patients, as it is believed that surgically returning the ventricle to its original dimensions is possible and associated with favorable outcomes. The purpose of this manuscript is to comprehensively review the current literature on various surgical strategies for ventricular restoration. We also contextualize the published data with respect to ventricular function, volume, structure, arrhythmias, mitral regurgitation, and clinical outcomes.
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http://dx.doi.org/10.1111/jocs.15968DOI Listing
September 2021

Synergetic Effects of Graphene Nanoplatelets/Tapioca Starch on Water-Based Drilling Muds: Enhancements in Rheological and Filtration Characteristics.

Polymers (Basel) 2021 Aug 10;13(16). Epub 2021 Aug 10.

Department of Petroleum Engineering, Universiti Teknologi PETRONAS, Seri Iskandar 32610, Malaysia.

Several borehole problems are encountered during drilling a well due to improper mud design. These problems are directly associated with the rheological and filtration properties of the fluid used during drilling. Thus, it is important to investigate the mud rheological and filtration characteristics of water-based drilling muds (WBMs). Several materials have been examined but due to the higher temperature conditions of wells, such materials have degraded and lost their primary functions. In this research, an attempt was made to prepare a water-based mud by utilizing graphene nano platelets (GNP) in addition to the native tapioca starch at different ratios. The combined effect of starch and graphene nano platelets has been investigated in terms of mud's rheological and filtration parameters, including its plastic viscosity (PV), yield point (YP), fluid loss volume (FLV) and filtercake thickness (FCT). The morphological changes in the filtercake have also been observed using Field Emission Scanning Electron Microscope (FESEM) micrographs. Plastic viscosity was increased from 18-35 cP, 22-31 cP and 21-28 cP for 68 °F, 250 °F and 300 °F, respectively. The yield point was also enhanced from 22-37 lb/100ft, 26-41 lb/100ft and 24-31 lb/100ft at the studied range. The fluid loss was dramatically reduced from 14.5-6.5 mL, 17.3-7.5 mL and 36-9.5 mL at 68 °F, 250 °F and 300 °F respectively. Similarly, filtercake thickness was also reduced which was further illustrated by filtercake morphology.
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http://dx.doi.org/10.3390/polym13162655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401484PMC
August 2021

Recent insights into pathophysiology and management of mechanical complications of myocardial infarction.

Curr Opin Cardiol 2021 Sep;36(5):623-629

Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, Calgary, Alberta.

Purpose Of Review: Mechanical complications of myocardial infarction are a group of postischemic events and include papillary muscle rupture resulting in ischemic mitral regurgitation, ventricular septal defect, left ventricle free wall rupture, pseudoaneurysm, and true aneurysm. Advances made in management strategies, such as the institution of 'Code STEMI' and percutaneous interventions, have lowered the incidence of these complications. However, their presentation is still associated with increased morbidity and mortality. Early diagnosis and appropriate management is crucial for facilitating better clinical outcomes.

Recent Findings: Although the exact timing of a curative intervention is not known, emerging percutaneous and transcatheter approaches and improving mechanical circulatory support (MCS) devices have greatly enhanced our ability to manage and treat some of the complications postinfarct.

Summary: Although the incidence of mechanical complications of myocardial infarction has decreased over the past few decades, these complications are still associated with high rates of morbidity and mortality. The combination of early and accurate diagnosis and subsequent appropriate management are imperative for optimizing clinical outcomes. Although more randomized clinical trials are needed, mechanical circulatory support devices and emerging therapeutic strategies can be offered to carefully selected patients.
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http://dx.doi.org/10.1097/HCO.0000000000000881DOI Listing
September 2021

A state-of-the-art review on spent coffee ground (SCG) pyrolysis for future biorefinery.

Chemosphere 2021 Jul 30;286(Pt 2):131730. Epub 2021 Jul 30.

Mechanical Engineering Department, College of Engineering, King Khalid University, P.O. Box 394, Abha, 61421, Saudi Arabia.

Coffee is a globally consumed beverage that produces a substantial amount of valuable organic waste known as spent coffee grounds (SCG). Although SCG is a non-edible biomass, research initiatives focused on valorizing/utilizing its organic content, protecting the environment, and reducing the high oxygen demand required for its natural degradation. The integration with biorefinery in general and with pyrolysis process in specific is considerered the most successful solid waste management strategy of SCG that produce energy and high-value products. This paper aims at providing a quantitative analysis and discussion of research work done over the last 20 years on SCG as a feedstock in the circular bioeconomy (CBE). Management stratigies of SCG have been thoroughly reviewed and pyrolysis process has been explored as a novel technology in CBE. Results revealed that explored articles belong to Chemical, physical., biological and environmental science branches, with Energy & Fuels as the most reporting themes. Published works correlate SCG to renewable energy, biofuel, and bio-oil, with pyrolysis as a potential valorization approach. Literature review showed that only one study focused on the pyrolysis of defatted spent coffee grounds (DSCG). The insightful conclusions of this paper could assist in proposing several paths to more economically valorization of SCG through biorefinery, where extracted oil can be converted to biofuels or value-added goods. It was highlighted the importance of focusing on the coupling of SCG with CBE as solid waste managment strategy.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131730DOI Listing
July 2021

Valorization of groundnut shell via pyrolysis: Product distribution, thermodynamic analysis, kinetic estimation, and artificial neural network modeling.

Chemosphere 2021 Nov 15;283:131162. Epub 2021 Jun 15.

Department of Chemical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi, United Arab Emirates. Electronic address:

Pyrolysis of agricultural biomass is a promising technique for producing renewable energy and effectively managing solid waste. In this study, groundnut shell (GNS) was processed at 500 °C in an inert gas atmosphere with a gas flow rate and a heating rate of 10 mL/min and 10 °C/min, respectively, in a custom-designed fluidized bed pyrolytic-reactor. Under optimal operating conditions, the GNS-derived pyrolytic-oil yield was 62.8 wt.%, with the corresponding biochar (19.5 wt.%) and biogas yields (17.7 wt.%). The GC-MS analysis of the GNS-based bio-oil confirmed the presence of (trifluoromethyl)pyridin-2-amine (18.814%), 2-Fluoroformyl-3,3,4,4-tetrafluoro-1,2-oxazetidine (16.23%), 5,7-dimethyl-1H-Indazole (11.613%), N-methyl-N-nitropropan-2-amine (6.5%) and butyl piperidino sulfone (5.668%) as major components, which are used as building blocks in the biofuel, pharmaceutical, and food industries. Furthermore, a 2 × 5 × 1 artificial neural network (ANN) architecture was developed to predict the decomposition behavior of GNS at heating rates of 5, 10, and 20 °C/min, while the thermodynamic and kinetic parameters were estimated using a non-isothermal model-free method. The Popescu method predicted activation energy (E) of GNS biomass ranging from 111 kJ/mol to 260 kJ/mol, with changes in enthalpy (ΔH), Gibbs-free energy (ΔG), and entropy (ΔS) ranging from 106 to 254 kJ/mol, 162-241 kJ/mol, and -0.0937 to 0.0598 kJ/mol/K, respectively. The extraction of high-quality precursors from GNS pyrolysis was demonstrated in this study, as well as the usefulness of the ANN technique for thermogravimetric analysis of biomass.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131162DOI Listing
November 2021

Delirium and depression in cardiac surgery: A comprehensive review of risk factors, pathophysiology, and management.

J Card Surg 2021 Aug 13;36(8):2876-2889. Epub 2021 Jun 13.

Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute, Calgary, Alberta, Canada.

Background: Mental health and wellbeing continue to gain more attention as they are inextricably associated with clinical outcomes, particularly quality of life. Many medical ailments and major surgeries affect patients' mental health, including depression and delirium.

Aims: The objective of this manuscript was to comprehensively review and critically examine the literature pertaining to cardiac surgery, depression, and delirium.

Methods: This is a narrative review article. We performed our search analysis by using the following key words: "Cardiac Surgery", "Depression", "Delirium", "Clinical outcomes", and "Mental Health". Search analysis was done on MedLine PubMed, accessing indexed peer-reviewed publications.

Results: Cardiac Surgery is a life-altering intervention indicated to improve morbidity and mortality in patients with cardiovascular diseases. Psychiatric conditions before and after cardiac surgery worsen patient prognosis and increase mortality rate. Specifically, preoperative depression increases postoperative depression and is associated with impaired functional status, slow physical recovery, and an increased readmission rate.

Discussion: Although the exact pathophysiology between depression and cardiovascular disease (CVD) is unknown, several pathways have been implicated. Unmanaged depression can also lead to other psychological conditions such as delirium. Like depression, the exact association between delirium and CVD is not well understood, but believed to be multifactorial.

Conclusion: Herein, we provide a comprehensive review of the links between depression, delirium, and cardiovascular surgery. We critically examine the current data that pertains to the pathophysiology of these debilitating mental health issues in the context of cardiac surgery. Finally, we summarize the various treatment options available for managing depression and delirium in the cardiac surgery patient population.
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http://dx.doi.org/10.1111/jocs.15610DOI Listing
August 2021

Robot-assisted coronary artery bypass surgery: a systematic review and meta-analysis of comparative studies.

Can J Surg 2020 Nov-Dec;63(6):E491-E508

From the Health Technology & Policy Unit, School of Public Health, University of Alberta, Edmonton, AB (Hammal, Nagase, Menon, Stafinski); the Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, AB (Ali); and the Division of Cardiac Surgery, Department of Surgery, Mazankowski Alberta HeartInstitute, University of Alberta, Edmonton, AB (Nagendran).

Background: Robot-assisted coronary bypass (RCAB) surgery has been proposed as an alternative to conventional coronary artery bypass grafting (C-CABG) for managing coronary heart disease, but the evidence on its performance compared to other existing treatments is unclear. The aim of this study was to assess, through a systematic review of comparative studies, the safety and clinical effectiveness of RCAB compared to C-CABG and other minimally invasive approaches for the treatment of coronary heart disease.

Methods: We conducted a systematic review of primary studies in the English-language literature comparing RCAB to existing treatment options (C-CABG, minimally invasive direct coronary artery bypass [MIDCAB] and port-access coronary artery bypass [PA-CAB]) following Cochrane Collaboration guidelines. Meta-analyses were performed where appropriate.

Results: We reviewed 13 studies: 11 primary studies of RCAB (v. C-CABG in 7, v. MIDCAB in 3 and v. PA-CAB in 1) and 2 multicentre database studies (RCAB v. non-RCAB). The overall quality of the evidence was low. Most studies showed no significant benefit of RCAB over other treatments in a majority of outcome variables. Meta-analyses showed that RCAB had lower rates of pneumonia or wound infection than C-CABG, and shorter intensive care unit length of stay than C-CABG or MIDCAB. Individual studies showed that RCAB had some better outcomes than C-CABG (ventilation time, transfusion, postoperative pain, hospital length of stay) or MIDCAB (transfusion, postoperative pain, time to return to normal activities, physical functioning and hospital length of stay). The review of the database studies showed that RCAB was statistically superior to non-RCAB approaches in postoperative pain, renal failure, transfusion, reoperation for bleeding, stroke and hospital length of stay; however, the difference between the 2 groups in several of these outcomes was small.

Conclusion: Although the findings from this review of comparative studies of RCAB appear promising and suggest that RCAB may offer some benefits to patients, in the absence of randomized controlled trials, these results should be interpreted cautiously.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747852PMC
February 2021

The Burden of Atherosclerotic Cardiovascular Disease in South Asians Residing in Canada: A Reflection From the South Asian Heart Alliance.

CJC Open 2019 Nov 30;1(6):271-281. Epub 2019 Oct 30.

Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.

South Asians (SAs), originating from the Indian subcontinent (India, Pakistan, Sri Lanka, Bangladesh, Nepal, and Bhutan), represent one quarter of the global population and are the largest visible minority in Canada. SAs experience the highest rates of coronary artery disease in Canada. Although conventional cardiovascular risk factors remain predictive in SA, the excess risk is not fully explained by these risk factors alone. Abdominal obesity, metabolic syndrome, and insulin resistance likely contribute a greater risk in SAs than in other populations. The South Asian Heart Alliance has been recently formed to investigate and recommend the best strategies for the prevention of cardiometabolic disease in SAs in Canada. This topic review represents a comprehensive overview of the magnitude of cardiovascular disease in SAs in Canada, with a review of conventional and novel risk markers in the SA population. Both primary and secondary prevention strategies are suggested and when possible, adapted specifically for the SA population. The need for SAs and their healthcare professionals to be more aware of the problem and potential solutions, along with the need for population-specific research, is highlighted.
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http://dx.doi.org/10.1016/j.cjco.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063609PMC
November 2019

Commentary: The promise of precision cardiovascular surgery.

J Thorac Cardiovasc Surg 2021 02 21;161(2):661-662. Epub 2019 Nov 21.

Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Libin Cardiovascular Institute, Calgary, Alberta, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2019.10.176DOI Listing
February 2021

Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein-Linked Extender Units in Ansamitocin Biosynthesis.

Chembiochem 2020 05 10;21(9):1309-1314. Epub 2020 Jan 10.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, 200240, Shanghai, P. R. China.

A few acyltransferase (AT) domains of modular polyketide synthases (PKSs) recruit acyl carrier protein (ACP)-linked extender units with unusual C2 substituents to confer functionalities that are not available in coenzyme A (CoA)-linked ones. In this study, an AT specific for methoxymalonyl (MOM)-ACP in the third module of the ansamitocin PKS was structurally and biochemically characterized. The AT uses a conserved tryptophan residue at the entrance of the substrate binding tunnel to discriminate between different carriers. A W275R mutation switches its carrier specificity from the ACP to the CoA molecule. The acyl-AT complex structures clearly show that the MOM-ACP accepted by the AT has the 2S instead of the opposite 2R stereochemistry that is predicted according to the biosynthetic derivation from a d-glycolytic intermediate. Together, these results reveal the structural basis of ATs recognizing ACP-linked extender units in polyketide biosynthesis.
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http://dx.doi.org/10.1002/cbic.201900628DOI Listing
May 2020

Immature platelet fraction as a useful marker in the etiological determination of thrombocytopenia.

Exp Hematol 2019 10 24;78:56-61. Epub 2019 Sep 24.

Centre for Bioscience, Manchester Metropolitan University, Manchester, UK. Electronic address:

The etiology of thrombocytopenia is important in treatment and management of the condition. Most platelet parameters that are routinely analyzed in the diagnostic laboratory have not proven useful in identifying the etiology, while specialized assays suffer from poor standardization and lack of agreement between laboratories. The immature platelet fraction (IPF), which indirectly provides a measure of bone marrow function, is showing promise as a valuable marker of thrombopoietic responses. This study set out determine whether the IPF could effectively identify specific underlying etiologies of thrombocytopenia in a large thrombocytopenic cohort, to allow for quicker, more effective management of the condition. The IPF was analyzed in a large cohort of 637 thrombocytopenic patients and 171 healthy control patients on the Sysmex XN 10 hematology analyzer using the specialized fluorescence optical analysis. The thrombocytopenic patients were divided into six cohorts based on etiology. The IPF% was significantly higher in cases of increased platelet consumption (median = 9.55, min = 1.1, max = 77.9) or pseudothrombocytopenia (median = 13.1, min = 0.4, max = 28.8) compared with control (median = 4.2, min = 1.3, max = 12.8). Furthermore, the IPF% was also able to identify idiopathic thrombocytopenic purpura (ITP) (p < 0.05) (median = 13.4, min = 2.8, max = 77.9) from other causes of increased platelet consumptive disorders (infection: median = 6.4, min = 1.1, max = 21.6; hemorrhage: median = 8.9, min = 1.2, max = 20.2). By use of this large thrombocytopenic cohort, the IPF% has been found to be of significant diagnostic value, providing a useful rapid test in the etiological investigation of platelet disorders.
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http://dx.doi.org/10.1016/j.exphem.2019.09.001DOI Listing
October 2019

Surgical Treatment for Ischemic Heart Failure (STICH) trial: A review of outcomes.

J Card Surg 2019 Oct 2;34(10):1075-1082. Epub 2019 Aug 2.

Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Canada.

Coronary artery disease (CAD) is a significant source of morbidity and mortality in developed countries. The landmark Surgical Treatment for Ischemic Heart Failure (STICH) trial has provided greatly needed evidence in the management of patients with severe left ventricle (LV) dysfunction (LVEF ≤ 35%) and CAD amenable to revascularization. The trial investigated two primary hypotheses: (i) that coronary artery bypass grafting (CABG) with optimal medical therapy (OMT) was superior to OMT alone, and (ii) that CABG with surgical ventricular reconstruction (SVR) would be superior to CABG alone. The results of the 10-year follow-up demonstrated significant long-term benefits with the addition of CABG to OMT. However, the second hypothesis yielded controversial results as the study found no difference between CABG with SVR and SVR alone. The STICH trial, and the numerous subanalyses that followed have reinforced and challenged a number of widely held beliefs regarding the management of patients with severe LV dysfunction and ischemic heart failure. The purpose of this comprehensive review is to outline the published data from the STICH trial and its substudies while providing a balanced assessment of the evidence-based conclusions and criticisms that have followed.
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http://dx.doi.org/10.1111/jocs.14166DOI Listing
October 2019

Structural Insights into the Substrate Specificity of Acyltransferases from Salinomycin Polyketide Synthase.

Biochemistry 2019 07 19;58(27):2978-2986. Epub 2019 Jun 19.

State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology , Shanghai Jiao Tong University , Shanghai 200240 , China.

Salinomycin with antibacterial and anticoccidial activities is a commercial polyether polyketide widely used in animal husbandry as a food additive. Malonyl-CoA (MCoA), methylmalonyl-CoA (MMCoA), and ethylmalonyl-CoA (EMCoA) are used as extension units in its biosynthesis. To understand how the salinomycin modular polyketide synthase (PKS) strictly discriminates among these extension units, the acyltransferase (AT) domains selecting MCoA, MMCoA, and EMCoA were structurally characterized. Molecular dynamics simulations of the AT structures helped to reveal the key interactions involved in enzyme-substrate recognitions, which enabled the engineering of AT mutants with switched specificity. The catalytic efficiencies ( k/ K) of these AT mutants are comparable with those of the wild-type AT domains. These results set the stage for engineering the AT substrate specificity of modular PKSs.
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http://dx.doi.org/10.1021/acs.biochem.9b00305DOI Listing
July 2019

Does prior coronary angioplasty affect outcomes of surgical coronary revascularization? Insights from the STICH trial.

Int J Cardiol 2019 09 15;291:36-41. Epub 2019 Mar 15.

Department of Medicine, University of Florida, Gainesville, FL, USA.

Background: The STICH trial showed superiority of coronary artery bypass plus medical treatment (CABG) over medical treatment alone (MED) in patients with left ventricular ejection fraction (LVEF) ≤35%. In previous publications, percutaneous coronary intervention (PCI) prior to CABG was associated with worse prognosis.

Objectives: The main purpose of this study was to analyse if prior PCI influenced outcomes in STICH.

Methods And Results: Patients in the STICH trial (n = 1212), followed for a median time of 9.8 years, were included in the present analyses. In the total population, 156 had a prior PCI (74 and 82, respectively, in the MED and CABG groups). In those with vs. without prior PCI, the adjusted hazard-ratios (aHRs) were 0.92 (95% CI = 0.74-1.15) for all-cause mortality, 0.85 (95% CI = 0.64-1.11) for CV mortality, and 1.43 (95% CI = 1.15-1.77) for CV hospitalization. In the group randomized to CABG without prior PCI, the aHRs were 0.82 (95% CI = 0.70-0.95) for all-cause mortality, 0.75 (95% CI = 0.62-0.90) for CV mortality and 0.67 (95% CI = 0.56-0.80) for CV hospitalization. In the group randomized to CABG with prior PCI, the aHRs were 0.76 (95% CI = 0.50-1.15) for all-cause mortality, 0.81 (95% CI = 0.49-1.36) for CV mortality and 0.61 (95% CI = 0.41-0.90) for CV hospitalization. There was no evidence of interaction between randomized treatment and prior PCI for any endpoint (all adjusted p > 0.05).

Conclusion: In the STICH trial, prior PCI did not affect the outcomes of patients whether they were treated medically or surgically, and the superiority of CABG over MED remained unchanged regardless of prior PCI.

Clinical Trial Registration: Clinicaltrials.gov; Identifier: NCT00023595.
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http://dx.doi.org/10.1016/j.ijcard.2019.03.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579621PMC
September 2019

Synergistic effect on co-pyrolysis of rice husk and sewage sludge by thermal behavior, kinetics, thermodynamic parameters and artificial neural network.

Waste Manag 2019 Feb 27;85:131-140. Epub 2018 Dec 27.

Chemical Engineering Department, University of Gujrat, Gujrat, Pakistan.

This study investigates the thermal decomposition, thermodynamic and kinetic behavior of rice-husk (R), sewage sludge (S) and their blends during co-pyrolysis using thermogravimetric analysis at a constant heating rate of 20 °C/min. Coats-Redfern integral method is applied to mass loss data by employing seventeen models of five major reaction mechanisms to calculate the kinetics and thermodynamic parameters. Two temperature regions: I (200-400 °C) and II (400-600 °C) are identified and best fitted with different models. Among all models, diffusion models show high activation energy with higher R(0.99) of rice husk (66.27-82.77 kJ/mol), sewage sludge (52.01-68.01 kJ/mol) and subsequent blends (45.10-65.81 kJ/mol) for region I and for rice husk (7.31-25.84 kJ/mol), sewage sludge (1.85-16.23 kJ/mol) and blends (4.95-16.32 kJ/mol) for region II, respectively. Thermodynamic parameters are calculated using kinetics data to assess the co-pyrolysis process enthalpy, Gibbs-free energy, and change in entropy. Artificial neural network (ANN) models are developed and employed on co-pyrolysis thermal decomposition data to study the reaction mechanism by calculating Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and coefficient of determination (R). The co-pyrolysis results from a thermal behavior and kinetics perspective are promising and the process is viable to recover organic materials more efficiently.
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http://dx.doi.org/10.1016/j.wasman.2018.12.031DOI Listing
February 2019

Society of Thoracic Surgeons Risk Score and EuroSCORE-2 Appropriately Assess 30-Day Postoperative Mortality in the STICH Trial and a Contemporary Cohort of Patients With Left Ventricular Dysfunction Undergoing Surgical Revascularization.

Circ Heart Fail 2018 11;11(11):e005531

Departments of Medicine, ontreal Heart Institute, University of Montreal, Canada (N.B., J.L.R.).

Background: The STICH trial (Surgical Treatment for Ischemic Heart Failure) demonstrated a survival benefit of coronary artery bypass grafting in patients with ischemic cardiomyopathy and left ventricular dysfunction. The Society of Thoracic Surgeons (STS) risk score and the EuroSCORE-2 (ES2) are used for risk assessment in cardiac surgery, with little information available about their accuracy in patients with left ventricular dysfunction. We assessed the ability of the STS score and ES2 to evaluate 30-day postoperative mortality risk in STICH and a contemporary cohort (CC) of patients with a left ventricle ejection fraction ≤35% undergoing coronary artery bypass grafting outside of a trial setting.

Methods And Results: The STS and ES2 scores were calculated for 814 STICH patients and 1246 consecutive patients in a CC. There were marked variations in 30-day postoperative mortality risk from 1 patient to another. The STS scores consistently calculated lower risk scores than ES2 (1.5 versus 2.9 for the CC and 0.9 versus 2.4 for the STICH cohort), and underestimated postoperative mortality risk. The STS and ES2 scores had moderately good C statistics: CC (0.727, 95% CI: 0.650-0.803 for STS, and 0.707, 95% CI: 0.620-0.795 for ES2); STICH (0.744, 95% CI: 0.677-0.812, for STS and 0.736, 95% CI: 0.665-0.808 for ES2). Despite the CC patients having higher STS and ES2 scores than STICH patients, mortality (3.5%) was lower than that of STICH (4.8%), suggesting a possible decrease in postoperative mortality over the past decade.

Conclusions: The 30-day postoperative mortality risk of coronary artery bypass grafting in patients with left ventricular dysfunction varies markedly. Both the STS and ES2 score are effective in evaluating risk, although the STS score tend to underestimate risk.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.118.005531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309904PMC
November 2018

Assays for Nucleotide Competitive Reversible and Irreversible Inhibitors of Ras GTPases.

Biochemistry 2018 08 11;57(31):4690-4699. Epub 2018 Jun 11.

Department of Structural Biochemistry , Max Planck Institute of Molecular Physiology , Otto-Hahn-Straße 11 , 44227 , Dortmund , Germany.

Although the Ras protein has been seen as a potential target for cancer therapy for the past 30 years, there was a tendency to consider it undruggable until recently. This has changed with the demonstration that small molecules with a specificity for (disease related mutants of) Ras can indeed be found, and some of these molecules form covalent adducts. A subgroup of these molecules can be characterized as competing with binding of the natural ligands GTP and GDP. Because of the distinct properties of Ras and related GTPases, in particular the very high nucleotide affinities and associated very low dissociation rates, assays for characterizing such molecules are not trivial. This is compounded by the fact that Ras family GTPases tend to be thermally unstable in the absence of a bound nucleotide. Here, we show that instead of using the unstable nucleotide-free Ras, the protein can be isolated as a 1:1 complex with a modified nucleotide (GDP-β-methyl ester) with low affinity to Ras. With this nucleotide analogue bound to the protein, testing of inhibitors is made experimentally more convenient and we present assays that allow the rapid assessment of the kinetic constants describing the inhibition process.
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http://dx.doi.org/10.1021/acs.biochem.8b00234DOI Listing
August 2018

Structure of the tandem PX-PH domains of Bem3 from Saccharomyces cerevisiae.

Acta Crystallogr F Struct Biol Commun 2018 05 24;74(Pt 5):315-321. Epub 2018 Apr 24.

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.

The structure of the tandem lipid-binding PX and pleckstrin-homology (PH) domains of the Cdc42 GTPase-activating protein Bem3 from Saccharomyces cerevisiae (strain S288c) has been determined to a resolution of 2.2 Å (R = 21.1%, R = 23.4%). It shows that the domains adopt a relative orientation that enables them to simultaneously bind to a membrane and suggests possible cooperativity in membrane binding.
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http://dx.doi.org/10.1107/S2053230X18005915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931145PMC
May 2018

Assessment of Blend PVDF Membranes, and the Effect of Polymer Concentration and Blend Composition.

Membranes (Basel) 2018 Mar 5;8(1). Epub 2018 Mar 5.

Center of Excellence in Desalination Technology, King Abdulaziz University, P.O. Box 80200, Jeddah 21589, Saudi Arabia.

In this work, PVDF homopolymer was blended with PVDF-co-HFP copolymer and studied in terms of morphology, porosity, pore size, hydrophobicity, permeability, and mechanical properties. Different solvents, namely N-Methyl-2 pyrrolidone (NMP), Tetrahydrofuran (THF), and Dimethylformamide (DMF) solvents, were used to fabricate blended PVDF flat sheet membranes without the introduction of any pore forming agent, through a non-solvent induced phase separation (NIPS) technique. Furthermore, the performance of the fabricated membranes was investigated for pressure and thermal driven applications. The porosity of the membranes was slightly increased with the increase in the overall content of PVDF and by the inclusion of PVDF copolymer. Total PVDF content, copolymer content, and mixed-solvent have a positive effect on mechanical properties. The addition of copolymer increased the hydrophobicity when the total PVDF content was 20%. At 25% and with the inclusion of mixed-solvent, the hydrophobicity was adversely affected. The permeability of the membranes increased with the increase in the overall content of PVDF. Mixed-solvents significantly improved permeability.
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http://dx.doi.org/10.3390/membranes8010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872195PMC
March 2018

Hospital variation in treatment and outcomes in acute coronary syndromes: Insights from the Alberta Contemporary Acute Coronary Syndrome Patients Invasive Treatment Strategies (COAPT) study.

Int J Cardiol 2017 Aug 5;241:70-75. Epub 2017 May 5.

Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Background: We examined variation in hospital treatment and its relationship to clinical outcome in a large population-based cohort of ACS patients within a single payer-government funded health care system.

Methods: Patients hospitalized in 106 hospitals in Alberta, Canada with a primary diagnosis of ACS were included (July 1, 2010-March 31, 2013) with comparisons made across the three cardiac catheterization-capable hospitals (Sites A-C). Cox proportional-hazard regression models were used to examine the multivariable-adjusted association between site and 1-year death or repeat cardiovascular (CV) hospitalization (primary endpoint).

Results: Of 14,155 patients, 1938 (13.7%) were admitted to a community hospital without transfer to an invasive hospital (10.7% in-hospital death). The remaining were admitted (n=4514, 36.9%) or transferred (n=7703, 63.1%) to an invasive hospital (A:5480; B:3621; C:3116) where 11,247 (92.1%) underwent catheterization. Comorbidities and angiographic disease burden differed across sites. Variation in 30-day revascularization (PCI: 71.3%, 72.0%, 68.7%, p<0.001; CABG: 6.2%, 6.4%, 9.3%, p<0.001) and drug-eluting stent use for PCI (24.3%, 54.6%, 50.5%, p<0.001) were observed. After adjustment for patient demographics and comorbidities, variation in rates of 1-year death or CV hospitalization was observed among those with 30-day revascularization (p(interaction)<0.001; B versus A: HR 0.78, 95%CI 0.66-0.91; C versus A: HR 0.77, 95%CI 0.65-0.91; B versus C: HR 1.01, 95%CI 0.84-1.21).

Conclusions: Despite a government funded health system, we have shown variation in hospital treatment exists. Following adjustment hospital site was associated with differences in clinical outcome within 1year. Hence, further efforts may be warranted to help address potential disparities in ACS care.
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http://dx.doi.org/10.1016/j.ijcard.2017.04.109DOI Listing
August 2017

Environment effects for earliness and grain yield traits in F diallel populations of maize (Zea mays L.).

J Sci Food Agric 2017 Oct 14;97(13):4408-4418. Epub 2017 Jun 14.

Department of Agricultural Sciences, University of Haripur, Haripur, Pakistan.

Background: Five maize inbred lines, 20 F diallel hybrids and two check genotypes were evaluated through genotype × environment interaction (GEI) and GGE biplot for earliness and yield traits at four locations.

Results: Genotype, environment and GEI showed highly significant differences for all the traits. In total sum of squares, environment and genotype played a primary role, followed by GEI. Larger effects of environment and genotype to total variation influence the earliness and yield traits. However, according to the GGE biplot, the first two principal components (PC1 and PC2) explained 95% of the variation caused by GEI. GGE biplot confirmed the differential response of genotypes across environments. F hybrid SWAJK-1 × FRHW-3 had better stability, with a good yield, and was considered an ideal genotype. F hybrid FRHW-2 × FRHW-1 showed more earliness at CCRI and Haripur, followed by PSEV3 × FRHW-2 and its reciprocal at Swat and Mansehra, respectively. F hybrids FRHW-1 × SWAJK-1, PSEV3 × SWAJK-1 and SWAJK-1 × FRHW-3 at Mansehra and Swat produced maximum grain yield, followed by SWAJK-1 × FRHW-1 and PSEV3 × FRHW-1 at Haripur and CCRI, respectively.

Conclusion: Overall, maize genotypes showed early maturity in plain areas (CCRI and Haripur) but higher yield in hilly areas (Mansehra and Swat). © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8420DOI Listing
October 2017

A comprehensive kinetics study of coconut shell waste pyrolysis.

Bioresour Technol 2017 Jul 18;235:1-11. Epub 2017 Mar 18.

Department of Industrial Engineering, King Abdulaziz University, Rabigh, Saudi Arabia.

Model-free and model-fitting methods were compared for pyrolytic conversion of the coconut shell waste. The apparent activation energy, estimated from differential and integral iso-conversional methods, increased with the progression of pyrolytic conversion. The reaction model, f(α)=(1-α)·[-ln(1-α)], indicate that order-based nucleation and growth mechanisms control the solid-state pyrolysis of the coconut shell waste. The active pyrolysis zone was consisted of overlapping multi-component degradation peaks. Average activation energy of the pseudo-components estimated from the Kissinger's method were 21.9kJ.mol, 106.4kJ.mol and 108.6kJ.mol for the dehydration, the degradation of pseudo-cellulose and pseudo-hemicellulose, respectively. Pseudo-lignin decomposed over a wide range of temperature with a slower conversion rate as compared to pseudo-hemicellulose and pseudo-cellulose. Average activation energy range of pseudo-lignin was estimated from the combination of model-free and model-fitting methods as 79.1-226.5kJ.mol.
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http://dx.doi.org/10.1016/j.biortech.2017.03.089DOI Listing
July 2017

Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

Circulation 2016 Nov 29;134(18):1314-1324. Epub 2016 Aug 29.

Duke Clinical Research Institute and Departments of Biostatistics and Bioinformatics (KLL) and Medicine (EJV), Duke University School of Medicine, Durham, North Carolina, USA.

Background: Advancing age is associated with a greater prevalence of coronary artery disease in heart failure with reduced ejection fraction and with a higher risk of complications after coronary artery bypass grafting (CABG). Whether the efficacy of CABG compared with medical therapy (MED) in patients with heart failure caused by ischemic cardiomyopathy is the same in patients of different ages is unknown.

Methods: A total of 1212 patients (median follow-up, 9.8 years) with ejection fraction ≤35% and coronary disease amenable to CABG were randomized to CABG or MED in the STICH trial (Surgical Treatment for Ischemic Heart Failure).

Results: Mean age at trial entry was 60 years; 12% were women; 36% were nonwhite; and the baseline ejection fraction was 28%. For the present analyses, patients were categorized by age quartiles: quartile 1, ≤54 years; quartile, 2 >54 and ≤60 years; quartile 3, >60 and ≤67 years; and quartile 4, >67 years. Older versus younger patients had more comorbidities. All-cause mortality was higher in older compared with younger patients assigned to MED (79% versus 60% for quartiles 4 and 1, respectively; log-rank P=0.005) and CABG (68% versus 48% for quartiles 4 and 1, respectively; log-rank P<0.001). In contrast, cardiovascular mortality was not statistically significantly different across the spectrum of age in the MED group (53% versus 49% for quartiles 4 and 1, respectively; log-rank P=0.388) or CABG group (39% versus 35% for quartiles 4 and 1, respectively; log-rank P=0.103). Cardiovascular deaths accounted for a greater proportion of deaths in the youngest versus oldest quartile (79% versus 62%). The effect of CABG versus MED on all-cause mortality tended to diminish with increasing age (P=0.062), whereas the benefit of CABG on cardiovascular mortality was consistent over all ages (P=0.307). There was a greater reduction in all-cause mortality or cardiovascular hospitalization with CABG versus MED in younger compared with older patients (P=0.004). In the CABG group, cardiopulmonary bypass time or days in intensive care did not differ for older versus younger patients.

Conclusions: CABG added to MED has a more substantial benefit on all-cause mortality and the combination of all-cause mortality and cardiovascular hospitalization in younger compared with older patients. CABG added to MED has a consistent beneficial effect on cardiovascular mortality regardless of age.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089908PMC
November 2016

Effects of Leaflet Design on Transvalvular Gradients of Bioprosthetic Heart Valves.

Cardiovasc Eng Technol 2016 12 29;7(4):363-373. Epub 2016 Aug 29.

Libin Cardiovascular Institute of Alberta, Health Research Innovation Centre (HRIC), University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.

Bioprosthetic aortic valves (BAVs) are becoming the prostheses of choice in heart valve replacement. The objective of this paper is to assess the effects of leaflet geometry on the mechanics and hemodynamics of BAVs in a fluid structure interaction model. The curvature and angle of leaflets were varied in 10 case studies whereby the following design parameters were altered: a circular arch, a line, and a parabola for the radial curvature, and a circular arch, a spline, and a parabola for the circumferential curvature. Six different leaflet angles (representative of the inclination of the leaflets toward the surrounding aortic wall) were analyzed. The 3-dimensional geometry of the models were created using SolidWorks, Pointwise was used for meshing, and Comsol Multiphysics was used for implicit finite element calculations. Realistic loading was enforced by considering the time-dependent strongly-coupled interaction between blood flow and leaflets. Higher mean pressure gradients as well as von Mises stresses were obtained with a parabolic or circular curvature for radial curvature or a parabolic or spline curvature for the circumferential curvature. A smaller leaflet angle was associated with a lower pressure gradient, and, a lower von Mises stress. The leaflet curvature and angle noticeably affected the speed of valve opening, and closing. When a parabola was used for circumferential or radial curvature, leaflets displacements were asymmetric, and they opened and closed more slowly. A circular circumferential leaflet curvature, a linear leaflet radial curvature, and leaflet inclination toward the surrounding aortic wall were associated with superior BAVs mechanics.
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http://dx.doi.org/10.1007/s13239-016-0279-5DOI Listing
December 2016

A pull-down procedure for the identification of unknown GEFs for small GTPases.

Small GTPases 2016 04 26;7(2):93-106. Epub 2016 Feb 26.

a Department of Structural Biochemistry , Max Planck Institute of Molecular Physiology , Dortmund , Germany.

Members of the family of small GTPases regulate a variety of important cellular functions. In order to accomplish this, tight temporal and spatial regulation is absolutely necessary. The two most important factors for this regulation are GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), the latter being responsible for the activation of the GTPase downstream pathways at the correct location and time. Although a large number of exchange factors have been identified, it is likely that a similarly large number remains unidentified. We have therefore developed a procedure to specifically enrich GEF proteins from biological samples making use of the high affinity binding of GEFs to nucleotide-free GTPases. In order to verify the results of these pull-down experiments, we have additionally developed two simple validation procedures: An in vitro transcription/translation system coupled with a GEF activity assay and a yeast two-hybrid screen for detection of GEFs. Although the procedures were established and tested using the Rab protein Sec4, the similar basic principle of action of all nucleotide exchange factors will allow the method to be used for identification of unknown GEFs of small GTPases in general.
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http://dx.doi.org/10.1080/21541248.2016.1156803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905258PMC
April 2016

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

CMAJ 2016 Mar 14;188(5):329-336. Epub 2015 Dec 14.

Population Health Research Institute (Walsh, Whitlock, Vincent, Rao-Melacini, Thabane, Devereaux), Hamilton, Ont.; McMaster University (Walsh, Whitlock, Syed, VanHelder, Guyatt, Rao-Melacini, Thabane, Devereaux), Hamilton, Ont.; London Health Sciences Centre (Garg, Lavi), Western University, London, Ont.; Dalhousie University (Légaré), Halifax, NS; Cleveland Clinic (Duncan, Nasr, Sessler), Cleveland, Ohio; Maine Medical Center (Zimmerman, Kramer), Portland, Me.; Wake Forest University (Miller, Gardner), Winston-Salem, NC; Sunnybrook Health Sciences Centre (Fremes), University of Toronto, Toronto, Ont.; University of Calgary (Kieser, Ali), Calgary, Alta.; All India Institute of Medical Sciences (Karthikeyan), New Delhi, India; The Chinese University of Hong Kong (Chan, Ho), Hong Kong SAR, China.

Background: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery.

Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization.

Results: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31).

Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery.

Trial Registration: ClinicalTrials.gov, no. NCT01071265.
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http://dx.doi.org/10.1503/cmaj.150632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786386PMC
March 2016

Symptomatic graft failure and impact on clinical outcome after coronary artery bypass grafting surgery: Results from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry.

Am Heart J 2015 Jun 13;169(6):833-40. Epub 2015 Mar 13.

Division of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Background: In contemporary coronary artery bypass graft (CABG) surgery, the association between symptomatic graft failure (GF) and long-term clinical outcome remains unclear. We sought to identify the clinical characteristics and outcomes of GF in symptomatic patients requiring cardiac catheterization within 1 year of CABG surgery.

Methods: Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease registry, 5,276 patients undergoing CABG surgery from September 2002 to August 2011 were identified. Clinical outcomes in patients with symptomatic GF were observed. Predictors of GF were analyzed at a graft level, whereas long-term survival was assessed at a patient level. A propensity score matching technique was used to adjust for baseline characteristics.

Results: Of our CABG cohort, 5.3% (281 patients [285 arterial and 653 vein grafts]) required symptom based coronary angiography within 1 year of CABG surgery. Acute coronary syndrome was the most common presentation (64.4%). At angiography, 27.0% (77/285) of arterial and 34.5% (225/653) of vein grafts were occluded. Respectively, arterial and vein GFs were treated as follows: percutaneous coronary intervention 61.0% versus 41.8%, re-do CABG 9.1% versus 0%, and medically without intervention 29.9% versus 58.2%. A strong trend toward reduced patient survival was noted with "arterial graft failure" (arterial ± vein GF) compared to "vein graft failure only" (no arterial GF) (adjusted hazard ratio 2.2, 95% CI 0.98-5.0, P = .056).

Conclusion: Although the rate of cardiac catheterization within 1 year of CABG is infrequent, these patients exhibit high GF rates and commonly present with an acute coronary syndrome. In addition, "arterial graft failure" compared to "vein graft failure only" confers a higher risk of adverse long-term survival.
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http://dx.doi.org/10.1016/j.ahj.2015.02.022DOI Listing
June 2015

Long-term survival with revascularization in South Asians admitted with an acute coronary syndrome (from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease Registry).

Am J Cardiol 2014 Aug 16;114(3):395-400. Epub 2014 May 16.

Division of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

People of South Asian (SA) descent are particularly susceptible to acute coronary syndromes (ACS). Yet, little information exists regarding their overall prognosis. The purpose of this study was to compare short- and long-term clinical outcomes of SA and European Canadians admitted with an ACS. Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease registry, 63,393 patients with ACS were reviewed (January 1999 to March 2012). After excluding Chinese patients, 1,825 SAs were compared with 60,791 European Canadians. Both groups were propensity matched, and outcomes were compared. Adjustment was performed using a 3:1 propensity matching technique. Adjusted 30-day and 1-year mortality rates were similar between SA and European patients with ACS (2.6% vs 2.7%, p = 0.93; 5.0% vs 4.8%, respectively, p = 0.75). Repeat angiography did not differ (9.9% vs 9.2%, p = 0.35), yet repeat revascularization within 1 year was greater in SA patients (9.8% vs 7.6%, p <0.01). Improved long-term survival (median 64 months, interquartile range 66 months) was noted with SA patients (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.71 to 0.95). In particular, long-term survival was observed in SA patients receiving coronary artery bypass grafting (HR 0.75, 95% CI 0.52 to 1.08) and percutaneous coronary intervention (HR 0.75, 95% CI 0.59 to 0.96). In conclusion, SA patients treated with revascularization appear to have improved long-term survival after ACS, compared with European Canadians. As such, clinicians should be cognitive of ethnic-based outcomes when determining therapeutic strategies in patient management.
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http://dx.doi.org/10.1016/j.amjcard.2014.04.051DOI Listing
August 2014

Cardiac signaling molecules and plasma biomarkers after cardiac transplantation: impact of tacrolimus versus cyclosporine.

J Heart Lung Transplant 2013 Dec;32(12):1222-32

Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada. Electronic address:

Background: We investigated cardiac proinflammatory, mitogenic, and apoptotic signaling events, and plasma biomarkers of inflammation and oxidative stress in de novo adult cardiac transplant (CTX) patients receiving tacrolimus (TAC) or cyclosporine A (CsA).

Methods: One hundred CTX recipients were randomized 1:1 to TAC/CsA in a prospective, randomized open-label multicenter study. Biomarkers of inflammation, immunity, oxidative stress, and cardiac signaling underlying growth and inflammation (extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase, mitogen-activated protein kinase kinases [MEK] 1/2 and 3/6, c-Src), and apoptosis and survival (c-Jun NH2-terminal kinases [JNK], Bax/Bcl2, Akt) were assessed at 2, 4, 12, 26, and 52 weeks post-CTX. Plasma from healthy controls (n = 30) and tissue from explanted non-failing hearts (n = 6) were used as controls.

Results: Biomarkers of inflammation/immunity (interleukin -6 and -18, soluble intercellular adhesion molecule, E-selectin, monocyte chemoattractant protein-1, osteopontin, fibrinogen, N-terminal prohormone brain natriuretic peptide, high-sensitive C-reactive protein) and oxidative stress (thiobarbituric acid reactive substances, nitrotyrosine) were increased, and antioxidant capacity was (glutathione/glutathione disulfide) decreased in patients vs healthy controls (p < 0.05). Phosphorylation of mitogen-activated protein kinases and Akt was increased, and Bax/Bcl was decreased in transplanted vs non-transplanted hearts. Except for plasma fibrinogen, which was lower in TAC vs. CsA, (p = 0.01), there were no significant differences in parameters studied between TAC vs CsA immunoprophylaxis.

Conclusions: De novo CTX recipients exhibit significant sub-clinical inflammation and oxidative stress that persists 12 months after transplantation. Associated with this is activation of myocardial growth and inflammatory signaling and decreased apoptosis. Our findings suggest that CTX is an inflammatory condition associated with oxidative stress and myocardial growth regardless of CsA or TAC immunoprophylaxis and independently of rejection status.
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http://dx.doi.org/10.1016/j.healun.2013.09.010DOI Listing
December 2013

Insights from the STICH trial: change in left ventricular size after coronary artery bypass grafting with and without surgical ventricular reconstruction.

J Thorac Cardiovasc Surg 2013 Nov 27;146(5):1139-1145.e6. Epub 2012 Oct 27.

Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY. Electronic address:

Objective: The present analysis of the Surgical Treatment for Ischemic Heart Failure randomized trial data examined the left ventricular volumes at baseline and 4 months after surgery to determine whether any magnitude of postoperative reduction in end-systolic volume affected survival after coronary artery bypass grafting alone compared with bypass grafting plus surgical ventricular reconstruction.

Methods: Of the 1000 patients randomized, 555 underwent an operation and had a paired imaging assessment with the same modality at baseline and 4 months postoperatively. Of the remaining 455 patients, 424 either died before the 4-month study or did not have paired imaging tests and were excluded, and 21 were not considered because they had died before surgery or did not receive surgery.

Results: Surgical ventricular reconstruction resulted in improved survival compared with coronary artery bypass grafting alone when the postoperative end-systolic volume index was 70 mL/m(2) or less. However, the opposite was true for patients achieving a postoperative volume index greater than 70 mL/m(2). A reduction in the end-systolic volume index of 30% or more compared with baseline was an infrequent event in both treatment groups and did not produce a statistically significant survival benefit with ventricular reconstruction.

Conclusions: In patients undergoing coronary artery bypass grafting plus surgical ventricular reconstruction, a survival benefit was realized compared with bypass alone, with the achievement of a postoperative end-systolic volume index of 70 mL/m(2) or less. Extensive ventricular remodeling at baseline might limit the ability of ventricular reconstruction to achieve a sufficient reduction in volume and clinical benefit.
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http://dx.doi.org/10.1016/j.jtcvs.2012.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810307PMC
November 2013
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