Mazankowski Alberta Heart Institute

Edmonton, Canada

Mazankowski Alberta Heart Institute

Edmonton, Canada
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News Article | November 29, 2016
Site: www.eurekalert.org

Heart medication taken in combination with chemotherapy reduces the risk of serious cardiovascular damage in patients with early-stage breast cancer, according to results from a new landmark clinical trial. Existing research has shown some cancer therapies such as Herceptin greatly improve survival rates for early-stage breast cancer, but come with a fivefold risk of heart failure -- a devastating condition as life-threatening as the cancer itself. A new five-year study, led by researchers at the University of Alberta and Alberta Health Services and funded by the Canadian Institutes of Health Research (CIHR) and Alberta Cancer Foundation, shows that two kinds of heart medications, beta blockers and ACE inhibitors, effectively prevent a drop in heart function from cancer treatment. "We think this is practice-changing," said Edith Pituskin, co-investigator of the MANTICORE trial. "This will improve the safety of the cancer treatment that we provide." Pituskin, an assistant professor in the Faculty of Nursing and Faculty of Medicine & Dentistry at the U of A, published their findings Nov. 28 in the Journal of Clinical Oncology. In the double-blind trial, 100 patients from Alberta and Manitoba with early-stage breast cancer were selected at random to receive either a beta blocker, ACE inhibitor or placebo for one year. Beta blockers and ACE inhibitors are drugs used to treat several conditions, including heart failure. Cardiac MRI images taken over a two-year period showed that patients who received the beta blockers showed fewer signs of heart weakening than the placebo group. The ACE inhibitor drug also had heart protection effects. Study lead Ian Paterson, a cardiologist at the Mazankowski Alberta Heart Institute and associate professor with the U of A's Department of Medicine, said these medications not only safeguard against damage to the heart, but may improve breast cancer survival rates by limiting interruptions to chemotherapy treatment. Any time a patient shows signs of heart weakening, he said, chemotherapy is stopped immediately, sometimes for a month or two months until heart function returns to normal. "We are aiming for two outcomes for these patients--we're hoping to prevent heart failure and we're hoping for them to receive all the chemotherapy that they are meant to get, when they are supposed to get it--to improve their odds of remission and survival." Patients with heart failure often experience fatigue, shortness of breath or even death, making it "an equally devastating disease with worse prognosis than breast cancer," Paterson said. Brenda Skanes has a history of cardiovascular problems in her family--her mom died of a stroke and her dad had a heart attack. She was eager to join the trial, both for her own health and the health of other breast cancer survivors. "I met survivors through my journey who experienced heart complications caused by Herceptin. If they had access to this, maybe they wouldn't have those conditions now," she said. "Me participating, it's for the other survivors who are just going into treatment." With two daughters of her own and a mother who lost her fight with colon cancer, study participant Debbie Cameron says she'd do anything to ensure prevent others from going through similar upheaval. "My daughters are always in the back of my mind and the what ifs--if they're diagnosed, what would make their treatment safer, better," Cameron said. "Anything I could do to make this easier for anybody else or give some insight to treatment down the road was, to me, a very easy decision." Pituskin said the study team, which also includes collaborators from the AHS Clinical Trials Unit at the Cross Cancer Institute and the University of Manitoba, represents a strong mix of research disciplines, particularly the oncology and cardiology groups. She said the results would not have been possible without funding support from CIHR and the Alberta Cancer Foundation. "Local people in Alberta supported a study that not only Albertans benefited from, but will change, again, the way care is delivered around the world." The results are expected to have a direct impact on clinical practice guidelines in Canada and beyond. "Every day in Canada, around 68 women are diagnosed with breast cancer. This discovery holds real promise for improving these women's quality of life and health outcomes," said Stephen Robbins, scientific director of CIHR's Cancer Research Institute. "We couldn't be more pleased with this return on our investment," said Myka Osinchuk, CEO of the Alberta Cancer Foundation. "This clinical research will improve treatment and make life better not only for Albertans facing cancer, but also for those around the world." Paterson said the research team is also investigating how to prevent heart complications in patients with other cancers, noting several other therapies have been linked to heart complications.


Wood P.W.,Mazankowski Alberta Heart Institute | Choy J.B.,Mazankowski Alberta Heart Institute | Nanda N.C.,University of Alabama at Birmingham | Becher H.,Mazankowski Alberta Heart Institute
Echocardiography | Year: 2014

Background and Methods In order to provide guidance for using measurements of left ventricular (LV) volume and ejection fraction (LVEF) from different echocardiographic methods a PubMed review was performed on studies that reported reference values in normal populations for two-dimensional (2D ECHO) and three-dimensional (3D ECHO) echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging (CMR). In addition all studies (2 multicenter, 16 single center) were reviewed, which included at least 30 patients, and the results compared of noncontrast and contrast 2D ECHO, and 3D ECHO with those of CMR. Results The lower limits for normal LVEF and the normal ranges for end-diastolic (EDV) and end-systolic (ESV) volumes were different in each method. Only minor differences in LVEF were found in studies comparing CMR and 2D contrast echocardiography or noncontrast 3D echocardiography. However, EDV and ESV measured with all echocardiographic methods were smaller and showed greater variability than those derived from CMR. Regarding agreement with CMR and reproducibility, all studies showed superiority of contrast 2D ECHO over noncontrast 2D ECHO and 3D ECHO over 2D ECHO. No final judgment can be made about the comparison between contrast 2D ECHO and noncontrast or contrast 3D ECHO. Conclusion Contrast 2D ECHO and noncontrast 3D ECHO show good reproducibility and good agreement with CMR measurements of LVEF. The agreement of volumes is worse. Further studies are required to assess the clinical value of contrast 3D ECHO as noncontrast 3D ECHO is only reliable in patients with good acoustic windows. © 2013 The Authors. Echocardiography published by Wiley Periodicals, Inc.


Brar S.,Divisions of General Internal Medicine | McAlister F.A.,Divisions of General Internal Medicine | McAlister F.A.,Mazankowski Alberta Heart Institute | McAlister F.A.,University of Alberta | And 3 more authors.
Circulation: Heart Failure | Year: 2013

BackgroundHeart failure is a common Emergency Department (ED) presentation but whether ED volume influences patient outcomes is unknown. Methods and ResultsRetrospective cohort of all adults presenting to 93 EDs between 1999 and 2009 with a most responsible diagnosis of heart failure (n=44 925 ED visits; mean age, 76.4 years). Cases seen in low-volume EDs had less comorbidities and were less likely to be hospitalized (54.5%) than those seen in medium (61.8%; adjusted odds ratio [aOR] 1.16, [95% confidence interval {CI} 1.10 1.23]) or high-volume EDs (73.6%; aOR, 1.95 [95% CI, 1.83 2.07]). Of patients treated and released, low-volume ED cases exhibited higher risk of death/hospitalization/ED visit in the subsequent 7 (22.0%) and 30 days (44.9%) than medium (16.3%; aOR, 0.81 [95% CI, 0.73 0.90], and 35.3%; aOR, 0.79 [95% CI, 0.73 0.86]) or high-volume ED cases (13.0%; aOR, 0.69 [95% CI, 0.61 0.78], and 30.2%; aOR, 0.67 [95% CI, 0.61 0.74]). Of patients hospitalized at the time of their index ED visit, low-volume ED cases exhibited a higher risk of 30-day death/all-cause readmission (24.3%) than those seen in medium (21.9%; aOR, 0.83 [95% CI, 0.76 0.91]) or high-volume EDs (18.1%; aOR, 0.77 [95% CI, 0.70 0.85]). ConclusionsLow-volume EDs were more likely to discharge patients with heart failure home, but low-volume ED cases exhibited worse outcomes (driven largely by readmissions or repeat ED visits). Interventions to improve management of acute heart failure are required at low-volume sites.


Tsuyuki R.T.,University of Alberta | Tsuyuki R.T.,Mazankowski Alberta Heart Institute | Al Hamarneh Y.N.,University of Alberta | Al Hamarneh Y.N.,Mazankowski Alberta Heart Institute | And 2 more authors.
Journal of the American College of Cardiology | Year: 2016

Background Despite the cardiovascular disease (CVD) risk associated with hypertension, diabetes, dyslipidemia, and smoking, these risk factors remain poorly identified and controlled. Objectives The study sought to evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk. Methods The RxEACH (Alberta Vascular Risk Reduction Community Pharmacy Project) study was a randomized trial conducted in 56 community pharmacies. Participants were recruited by their pharmacist, who enrolled adults at high risk for CVD. Patients were randomized to usual care (usual pharmacist care with no specific intervention) or intervention, comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education. Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets. Subjects received monthly follow-up visits for 3 months. The primary outcome was difference in change in estimated CVD risk between groups at 3 months. CVD risk was estimated using the greater of the Framingham, International, or United Kingdom Prospective Diabetes Study risk scores. Results We enrolled 723 patients (mean 62 years of age; 58% male, and 27% smokers). After adjusting for baseline values and center effect, there was a 21% difference in change in risk for CVD events (p < 0.001) between the intervention and usual care groups. The intervention group had greater improvements in low-density lipoprotein cholesterol (–0.2 mmol/l; p < 0.001), systolic blood pressure (–9.37 mm Hg; p < 0.001), glycosylated hemoglobin (–0.92%; p < 0.001), and smoking cessation (20.2%; p = 0.002). Conclusions The RxEACH study was the first large randomized trial of CVD risk reduction by community pharmacists, demonstrating a significant reduction in risk for CVD events. Engagement of community pharmacists with an expanded scope of practice could have significant public health implications. (The Alberta Vascular Risk Reduction Community Pharmacy Project: RxEACH [RxEACH]; NCT01979471) © 2016 American College of Cardiology Foundation


Ezekowitz J.A.,Mazankowski Alberta Heart Institute | Ezekowitz J.A.,University of Alberta
Current Cardiology Reports | Year: 2013

Acute heart failure is a public health issue with morbidity and mortality exceeding that of myocardial infarction. Novel compounds for the treatment of acute heart failure are clearly needed and fall into the general categories of inotropic, vasodilatory and other compounds in phase I to III of development. Furthest along are omecamtiv mecarbil (a cardiac myosin activator), ularitide (a natriuretic and diuretic peptide) and relaxin (a vasodilator). Each compound has a unique set of assets and liabilities that will aid in the understanding of the syndrome and application to the right patients at the right time in this heterogeneous syndrome. This review will explore current and future novel pharmacologic therapies for the treatment of acute heart failure. © Springer Science+Business Media New York 2013.


Alexopoulos N.,Athens Euroclinic | Katritsis D.,Athens Euroclinic | Raggi P.,University of Alberta | Raggi P.,Mazankowski Alberta Heart Institute
Atherosclerosis | Year: 2014

The current epidemic of obesity with the associated increasing incidence of insulin resistance, diabetes mellitus and atherosclerosis affecting a large proportion of the North American and Western populations, has generated a strong interest in the potential role of visceral adipose tissue in the development of atherosclerosis and its complications. The intra-abdominal and epicardial space are two compartments that contain visceral adipose tissue with a similar embryological origin. These visceral fats are highly inflamed in obese patients, patients with the metabolic syndrome and in those with established coronary artery disease; additionally they are capable of secreting large quantities of pro-inflammatory cytokines and free fatty acids. There is accumulating evidence to support a direct involvement of these regional adipose tissue deposits in the development of atherosclerosis and its complicating events, as will be reviewed in this article. © 2014 Elsevier Ireland Ltd.


Kienesberger P.C.,Mazankowski Alberta Heart Institute | Kienesberger P.C.,University of Alberta | Pulinilkunnil T.,Mazankowski Alberta Heart Institute | Pulinilkunnil T.,University of Alberta | And 4 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Myocardial triacylglycerol (TAG) constitutes a highly dynamic fatty acid (FA) storage pool that can be used for an energy reserve in the cardiomyocyte. However, derangements in myocardial TAG metabolism and accumulation are commonly associated with cardiac disease, suggesting an important role of intramyocardial TAG turnover in the regulation of cardiac function. In cardiomyocytes, TAG is synthesized by acyltransferases and phosphatases at the sarcoplasmic reticulum and mitochondrial membrane and then packaged into cytosolic lipid droplets for temporary storage or into lipoproteins for secretion. A complex interplay among lipases, lipase regulatory proteins, and lipid droplet scaffold proteins leads to the controlled release of FAs from the cardiac TAG pool for subsequent mitochondrial β-oxidation and energy production. With the identification and characterization of proteins involved in myocardial TAG metabolism as well as the identification of the importance of cardiac TAG turnover, it is now evident that adequate regulation of myocardial TAG metabolism is critical for both cardiac energy metabolism and function. In this article, we review the current understanding of myocardial TAG metabolism and discuss the potential role of myocardial TAG turnover in cardiac health and disease.This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". © 2012 Elsevier Ltd.


Barry A.R.,Mazankowski Alberta Heart Institute | Graham M.M.,University of Alberta
Journal of Cardiology Cases | Year: 2013

Clenbuterol is an oral β2-agonist utilized as an illicit substance for performance-enhancement or weight loss. We report a case of a 23-year-old male who presented with anxiety and chest tightness after intentional ingestion of 5000. μg of clenbuterol (125 times the recommended adult dose) to lose weight. His electrocardiogram showed sinus tachycardia and diffuse nonspecific repolarization abnormalities with mild inferolateral ST-segment depression. Bloodwork revealed a potassium of 2.0. mmol/L, peak lactate of 9.4. mmol/L, and peak troponin of 5.39. μg/L. A transthoracic echocardiogram was normal except for hyperdynamic left ventricular function. He was treated with intravenous fluids and oral metoprolol. His tachycardia and electrocardiogram abnormalities resolved after 48. h. Clenbuterol has gained notoriety in recent years as a drug of abuse and cases of toxicity will likely continue to increase due to its relative attainability and readily accessible online dosing information. Patients often present with agitation, palpitations, tachycardia, hypokalemia, and hyperglycemia. Treatment is supportive with intravenous fluids, β-blockers, and potassium supplementation.<. Learning objective: Clenbuterol, an oral β2-agonist, can be utilized as an illicit substance for performance-enhancement or weight loss. Cardiac toxicity and type II myocardial infarction can occur with clenbuterol overdoses. Associated symptoms include agitation, palpitations, tachycardia, hypokalemia, and hyperglycemia. Treatment is supportive primarily with intravenous fluid, β-blockers, and potassium supplementation.>. © 2013 Japanese College of Cardiology.


Chakrabarti S.,University of Alberta | Chakrabarti S.,Mazankowski Alberta Heart Institute | Davidge S.T.,University of Alberta | Davidge S.T.,Mazankowski Alberta Heart Institute
PLoS ONE | Year: 2012

Estrogen, the female sex hormone, is known to exert anti-inflammatory and anti-atherogenic effects. Traditionally, estrogen effects were believed to be largely mediated through the classical estrogen receptors (ERs). However, there is increasing evidence that G-protein coupled receptor 30 (GPR30), a novel estrogen receptor, can mediate many estrogenic effects on the vasculature. Despite this, the localization and functional significance of GPR30 in the human vascular endothelium remains poorly understood. Given this background, we examined the subcellular location and potential anti-inflammatory roles of GPR30 using human umbilical vein endothelial cells as a model system. Inflammatory changes were induced by treatment with tumor necrosis factor (TNF), a pro-inflammatory cytokine involved in atherogenesis and many other inflammatory conditions. We found that GPR30 was located predominantly in the endothelial cell nuclei. Treatment with the selective GPR30 agonist G-1 partially attenuated the TNF induced upregulation of pro-inflammatory proteins such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was completely abolished by the selective GPR30 antagonist G-15, suggesting that it was indeed mediated in a GPR30 dependent manner. Interestingly, estrogen alone had no effects on TNF-treated endothelium. Concomitant activation of the classical ERs blocked the anti-inflammatory effects of G-1, indicating opposing effects of GPR30 and the classical ERs. Our findings demonstrate that endothelial GPR30 is a novel regulator of the inflammatory response which could be a potential therapeutic target against atherosclerosis and other inflammatory diseases. © 2012 Chakrabarti, Davidge.


Dolinsky V.W.,Diabet Res Envisioned And Accomplished In Manitoba Res Theme Of The Manitoba Institute Of Child Hlth | Dyck J.R.B.,Mazankowski Alberta Heart Institute
Molecules | Year: 2014

Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

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