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Fitchett D.H.,University of Toronto | Mancini G.B.J.,University of British Columbia | Gregoire J.,Montreal Heart Institute | Anderson T.,University of Calgary | McPherson R.,Ottawa Heart Institute
Canadian Journal of Cardiology | Year: 2014

Decisions for statin therapy in the primary prevention of atherosclerotic cardiovascular disease are generally made using the 10-year Framingham Risk Score (FRS). Even when a family history of premature cardiovascular disease is taken into account, there is often ambiguity about the need for statin therapy for patients with a 10-year FRS of 5%-19% and low-density lipoprotein cholesterol <3.5 mmol/L. Current Canadian dyslipidemia guidelines recommend consideration of a diversity of other factors, including biochemical measurements and imaging studies to help determine whether the calculated FRS might be misleadingly low and whether statin therapy might, therefore, be prudent. However, efficient use of the plethora of secondary factors makes this decision process itself potentially ambiguous. This brief summary provides a practical approach for using clinical information, basic biochemical tests, and more specialized tests, such as carotid ultrasound and coronary artery calcium scoring, to identify groups of patients at greater risk for atherosclerotic cardiovascular disease than suggested by the FRS. © 2014 Canadian Cardiovascular Society.

Mascall K.S.,University of Aberdeen | Small G.R.,University of Aberdeen | Small G.R.,Ottawa Heart Institute | Gibson G.,University of Aberdeen | Nixon G.F.,University of Aberdeen
Journal of Cell Science | Year: 2012

Following myocardial infarction, angiogenesis occurs as a result of thrombus formation, which permits reperfusion of damaged myocardium. Sphingosine 1-phosphate (S1P) is a naturally occurring lipid mediator released from platelets and is found in high concentrations at sites of thrombosis. S1P might therefore be involved in regulating angiogenesis following myocardial infarction and might influence reperfusion. The aims of this study were to determine the effects of S1P in human coronary arterial cell angiogenesis and delineate the subsequent mechanisms. An in vitro model of angiogenesis was developed using a co-culture of human coronary artery endothelial cells, human coronary smooth muscle cells and human fibroblasts. In this model, S1P inhibited angiogenesis and this was dependent on the presence of smooth muscle cells. The mechanism of the inhibitory effect was through S1P-induced release of a soluble mediator from smooth muscle cells. This mediator was identified as tissue inhibitor of metalloproteinase-2 (TIMP-2). Release of TIMP-2 was dependent on S1P-induced activation of Rho kinase and directly contributed to incomplete formation of endothelial cell adherens junctions. This was observed as a diffuse localisation of VE-cadherin, leading to decreased tubulogenesis. A similar inhibitory response to S1P was demonstrated in an ex vivo human arterial model of angiogenesis. In summary, S1P-induced inhibition of angiogenesis in human artery endothelial cells is mediated by TIMP-2 from vascular smooth muscle cells. This reduces the integrity of intercellular junctions between nascent endothelial cells. S1P might therefore inhibit the angiogenic response following myocardial infarction. © 2012.

Cosme J.,University of Toronto | Liu P.P.,University of Toronto | Liu P.P.,Toronto General Research Institute | Liu P.P.,Ottawa Heart Institute | And 2 more authors.
Proteomics | Year: 2013

The exosome is a secreted microvesicle that has been shown to contain genetic material and proteins and is involved in multiple levels of cellular communication. The cardiovascular exosome proteome is a promising subproteome that warrants investigation since a detailed understanding of its role in the heart should improve our comprehension of intercellular communication in the heart, and may even assist in biomarker discovery. Indeed, uncovering the role of the exosome in cardiovascular physiology could be accomplished with the application of scientific approaches and insights gained from studies of exosomes in other fields, such as cancer biology and immunology, where much of the established knowledge of the exosome has been generated. In the present review, we discuss the relevant literature and examine areas of investigation that would bring the cardiovascular exosome to the forefront of intercellular communication in the heart. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morillo C.A.,Hamilton Health Sciences | Verma A.,Southlake Regional Health Center | Connolly S.J.,Hamilton Health Sciences | Nair G.M.,Ottawa Heart Institute | And 5 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Atrial fibrillation (AF) is the most common rhythm disorder seen in clinical practice. Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF. Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed; however, its role as a first-line therapy needs further investigation. OBJECTIVE: To compare radiofrequency ablation with antiarrhythmic drugs (standard therapy) in treating patients with paroxysmal AF as a first-line therapy. DESIGN, SETTING, AND PATIENTS: A randomized clinical trial involving 127 treatment-naive patients with paroxysmal AF were randomized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation. The first patient was enrolled July 27, 2006; the last patient, January 29, 2010. The last follow-up was February 16, 2012. INTERVENTIONS: Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months. MAIN OUTCOMES AND MEASURES: The time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip, was the primary outcome. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool. RESULTS: Forty-four patients (72.1%) in the antiarrhythmic group and in 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = .02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = .03). No deaths or strokes were reported in either group; 4 cases of cardiac tamponade were reported in the ablation group. In the standard treatment group, 26 patients (43%) underwent ablation after 1-year. Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up. However, improvement was not significantly different among groups. CONCLUSIONS AND RELEVANCE: Among patients with paroxysmal AF without previous antiarrhythmic drug treatment, radiofrequency ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at 2 years. However, recurrence was frequent in both groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00392054 Copyright 2014 American Medical Association. All rights reserved.

Lustig D.B.,University of Ottawa | Lustig D.B.,Ottawa Hospital Research Institute | Rodriguez R.,Ottawa Heart Institute | Wells P.S.,University of Ottawa | Wells P.S.,Ottawa Hospital Research Institute
Thrombosis Research | Year: 2015

Background Cancer patients have a significantly higher risk of developing a venous thromboembolism (VTE) compared to non-cancer patients and yet studies suggest VTE risk among ambulatory cancer patients varies widely. Recently, predictive models capable of risk-stratifying a broad range of ambulatory cancer outpatients have been developed. Using the Khorana model a score of 2 was intermediate-high risk for VTE as reported by Ay and colleagues. However, validation in a broader population and methods to implement this model seamlessly into clinical practice are lacking. Objective To create and assess the feasibility of an innovative computerized Care Process Management System (CPMS) that would automatically access electronic medical records to calculate in real-time the risk of VTE in patients with active cancer using an established VTE risk scoring system. Methods A prospective observational study of all newly referred cancer patients at the Ottawa Regional Cancer Center, the sole cancer care provider for 1.2 million inhabitants, was conducted. Results 699 new referrals were determined to have a cancer diagnosis for the first time as identified by the computer software and qualified for our study and 580 were eligible. In total 25% had intermediate-high risk for VTE and during the 3-month follow up period, 16 of the 143 (11%) developed a VTE which further validates the Khorana model for identifying intermediate-high risk patients. Of the 437 patients in the low risk group 19 (4%) developed a VTE. Conclusion Newly diagnosed cancer patients can be readily stratified into intermediate-high and low risk of VTE using our novel CPMS system. This innovative tool can be used to facilitate customized management decisions regarding VTE prophylaxis for intermediate-high risk patients based their individual risk factors. © 2015 Elsevier Ltd. All rights reserved.

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