Peter Munk Cardiac Center

Canada

Peter Munk Cardiac Center

Canada
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Moayedi Y.,A+ Network | Ross H.J.,Peter Munk Cardiac Center
Clinical Science | Year: 2017

The purpose of this review is to provide an overview of diagnosis, prognosis and management of heart failure (HF) with reduced ejection fraction (HFrEF). Specifically, this review is divided into three sections. The first section will address biomarkers. The discovery of biomarkers has allowed further understanding of the pathophysiology of HF and provides insight into potential therapeutic targets. This review will focus on novel applications of natriuretic peptides (NPs) in clinical trials. Next, emerging biomarkers of HF, such as ST2, galectin-3 and copeptin, will be discussed. The second section aims to highlight HF therapies, including novel drugs and durable devices. The last section will review home haemodynamic monitoring and mobile health. We aim to provide context for the understanding of novel diagnostic and therapeutic advances in HF that are still in phase II or III trials, and have yet to become widely available. © 2017. Biochemical Society. All rights reserved.


Greig D.,Peter Munk Cardiac Center | Greig D.,University of Toronto | Greig D.,University of Santiago de Chile | Austin P.C.,University of Toronto | And 14 more authors.
Circulation: Heart Failure | Year: 2014

Background-Identification of coronary ischemia may enable targeted diagnostic and therapeutic strategies for acute heart failure. We determined the risk of 30-day mortality associated with ischemic ECG abnormalities in patients with acute heart failure. Methods and Results-Among 8772 patients (53.4% women, median 78 years [Q1, Q3: 68,84]) presenting with acute heart failure to 86 hospital emergency departments in Ontario, Canada, Q-waves, T-wave inversion, or ST-depression were present in 51.8% of subjects. However, presence of ST-depression was the only finding associated with 30-day mortality with adjusted odds ratio 1.24 (95% confidence interval [CI], 1.02-1.50). Using continuous net reclassification improvement, addition of ST-depression to the Emergency Heart failure Mortality Risk Grade model reclassified 16.9% of patients overall, and 29.3% of those with a history of ischemic heart disease (both P<0.001). By adding STdepression to the model, the Emergency Heart failure Mortality Risk Grade was extended to predict 30-day death with high discrimination (c-statistic 0.801), with 0.57% mortality rate in the lowest risk decile. Adjusted odds ratios for 30-day mortality were 2.81 (95% CI, 1.48-5.31; P=0.002) in quintile 2, 7.41 (95% CI, 4.13-13.30; P<0.001) in quintile 3, and 14.47 (95% CI, 8.20-25.54; P<0.001) in quintile 4 compared with the lowest risk quintile. When the highest risk quintile was subdivided into 2 equally sized risk strata (deciles 9 and 10), the adjusted odds ratios for 30-day mortality were 27.20 (95% CI, 15.33-48.27; P<0.001) in decile 9 and 58.96 (95% CI, 33.54-103.65; P<0.001) in highest risk decile 10. Conclusions-Presence of ST-depression on the ECG reclassified risk of 30-day mortality in patients with acute heart failure, identifying both high- and low-risk subsets. © 2014 American Heart Association, Inc.


Degousee N.,University of Toronto | Simpson J.,University of Toronto | Scholich K.,Institute For Klinische Pharmakologie | Angoulvant D.,University of Tours | And 12 more authors.
Circulation | Year: 2012

Background-Microsomal prostaglandin E 2 synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E 2 biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges -/- mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges ++ mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation. Methods and Results-Cardiac structure and function in Ptges ++ mice with Ptges ++ bone marrow (BM) and Ptges ++ mice with Ptges -/- BM (BM -/-) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM -/- mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM ++ mice. BM -/- mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM ++ mice. Levels of prostaglandin E 2 were higher in the infarct and viable myocardium of BM -/- mice than in BM ++ mice. Conclusions-Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E 2 biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction. © 2012 American Heart Association, Inc.


PubMed | Astrazeneca, Peter Munk Cardiac Center, Albert Ludwigs University of Freiburg and Harvard University
Type: Comparative Study | Journal: Basic research in cardiology | Year: 2016

Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL-3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression.


PubMed | University of Toronto, e Cancer Clinical Research Unit CCRU, Peter Munk Cardiac Center, University of Ottawa and Toronto General Hospital
Type: Journal Article | Journal: Psychology, health & medicine | Year: 2016

Stigma appears to influence emotional distress and well-being in cancer survivors, but cross-cultural differences have been ignored. Previous studies suggest that stigma may be especially relevant for survivors of Asian origin. However, their study designs (e.g. focused on female cancers, qualitative designs, and an absence of comparison groups) limit the strength of this conclusion. We hypothesized that (1) Asian-born Chinese immigrants (AI) would report more perceived cancer-related stigma than Western-born Caucasians (WBC); and (2) the impact of stigma on emotional distress and well-being would be greater in AI as compared to WBC. Head and neck cancer survivors (n=118 AI and n=404 WBC) completed measures of well-being, emotional distress, and a three-item indicator of stigma in structured interviews. The majority of respondents (59%) reported one or more indicators of stigma. Stigma correlated significantly with emotional distress (r=.13, p=.004) and well-being (r=-.09, p=.032). Contrary to our hypotheses, WBCs and AIs did not differ in reported stigma nor did we detect differences in its psychosocial impact. Stigma exerts a deleterious psychosocial impact on head and neck cancer survivors. It did not differ significantly between AI and WBC survivors.


Garg V.,Peter Munk Cardiac Center | Ouzounian M.,Peter Munk Cardiac Center | Peterson M.D.,University of Toronto
Current Opinion in Cardiology | Year: 2016

Purpose of review: The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. Recent findings As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Summary Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Moazami N.,Cleveland Clinic | Steffen R.J.,Cleveland Clinic | Naka Y.,Columbia University | Jorde U.,Columbia University | And 7 more authors.
Annals of Thoracic Surgery | Year: 2014

Background The DuraHeart is a continuous centrifugal-flow left ventricular assist device that uses active magnetic levitation for impeller positioning designed for improved hemocompatibility and durability. This study reviews the results of the US trial with specific attention to hemolysis, thrombotic complications, and pump failure. Methods The US SUSTAIN trial was a multicenter, prospective, single-arm observational study in advanced heart failure patients listed for transplantation. Follow-up was complete in 100% of the patients at 6 months. Results Sixty-three patients were enrolled at 23 centers. Forty-six patients (73%) reached the primary end points of survival to transplantation, alive on the original device at 180 days and listed for transplantation, or explant for recovery. Median duration of support was 267 days (range, 10 to 952 days) with a total support time of 46 patient-years. There was no clinical hemolysis reported during the study. Mean lactate dehydrogenase values peaked at day 4 and significantly decreased during support (435 ± 236 U/L and 297 ± 142 U/L on day 3 and day 180, respectively). There were no cases of pump thrombosis reported, and 3 cases of pump thrombus "in transit" (0.06 events/patient-year) were observed. There were 6 (10%) cases of magnetic levitation system failure, all secondary to cable wire fractures (0.12 events/patient-year). All patients were hemodynamically stable with the backup hydrodynamic mode. Major adverse events included gastrointestinal bleeding (0.52 events/patient-year), ischemic and hemorrhagic strokes (0.17 events/patient-year and 0.09 events/patient-year, respectively), and driveline infections (0.67 events/patient-year). Conclusions The DuraHeart demonstrated good hemocompatibility; however, the reliability of full magnetic levitation systems should be a high priority in future pump designs. © 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc.


Feindel C.M.,Peter Munk Cardiac Center | Ouzounian M.,Dalhousie University | Latham T.B.,Royal Columbian Hospital | Hendry P.,University of Ottawa | And 6 more authors.
Canadian Journal of Cardiology | Year: 2012

As the professional society representing cardiac surgeons in Canada, the Canadian Society of Cardiac Surgeons (CSCS) recognizes the importance of maintaining a stable cardiac surgical workforce. The current reactive approach to health human resource management in cardiac surgery is inadequate and may result in significant misalignment of cardiac surgeon supply and demand. The availability of forecasting models and high quality, consistent data on productivity, workload, utilization, and demand is a prerequisite for our profession's capacity to predict and plan for changes in health human resources. The CSCS recognizes that improved workforce management is a key component to providing optimal cardiac surgical care for Canadians in the future and has developed the recommendations in this document as a call to action to interested stakeholders and policymakers to bring substantial improvements to health human resource management in cardiac surgery. © 2012 Canadian Cardiovascular Society.


PubMed | Peter Munk Cardiac Center
Type: Comparative Study | Journal: The Canadian journal of cardiology | Year: 2012

As the professional society representing cardiac surgeons in Canada, the Canadian Society of Cardiac Surgeons (CSCS) recognizes the importance of maintaining a stable cardiac surgical workforce. The current reactive approach to health human resource management in cardiac surgery is inadequate and may result in significant misalignment of cardiac surgeon supply and demand. The availability of forecasting models and high quality, consistent data on productivity, workload, utilization, and demand is a prerequisite for our professions capacity to predict and plan for changes in health human resources. The CSCS recognizes that improved workforce management is a key component to providing optimal cardiac surgical care for Canadians in the future and has developed the recommendations in this document as a call to action to interested stakeholders and policymakers to bring substantial improvements to health human resource management in cardiac surgery.


PubMed | Peter Munk Cardiac Center, Terumo Heart Inc, Cleveland Clinic, Newark Beth Israel Medical Center and 3 more.
Type: Clinical Trial | Journal: The Annals of thoracic surgery | Year: 2014

The DuraHeart is a continuous centrifugal-flow left ventricular assist device that uses active magnetic levitation for impeller positioning designed for improved hemocompatibility and durability. This study reviews the results of the US trial with specific attention to hemolysis, thrombotic complications, and pump failure.The US SUSTAIN trial was a multicenter, prospective, single-arm observational study in advanced heart failure patients listed for transplantation. Follow-up was complete in 100% of the patients at 6 months.Sixty-three patients were enrolled at 23 centers. Forty-six patients (73%) reached the primary end points of survival to transplantation, alive on the original device at 180 days and listed for transplantation, or explant for recovery. Median duration of support was 267 days (range, 10 to 952 days) with a total support time of 46 patient-years. There was no clinical hemolysis reported during the study. Mean lactate dehydrogenase values peaked at day 4 and significantly decreased during support (435236 U/L and 297142 U/L on day 3 and day 180, respectively). There were no cases of pump thrombosis reported, and 3 cases of pump thrombus in transit (0.06 events/patient-year) were observed. There were 6 (10%) cases of magnetic levitation system failure, all secondary to cable wire fractures (0.12 events/patient-year). All patients were hemodynamically stable with the backup hydrodynamic mode. Major adverse events included gastrointestinal bleeding (0.52 events/patient-year), ischemic and hemorrhagic strokes (0.17 events/patient-year and 0.09 events/patient-year, respectively), and driveline infections (0.67 events/patient-year).The DuraHeart demonstrated good hemocompatibility; however, the reliability of full magnetic levitation systems should be a high priority in future pump designs.

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