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The Translational Sciences Team


The Translational Science team is led by Dr. Philip Joseph of the Population Health Research Institute, McMaster University, Hamilton, ON, Canada, and by Dr. Eileen O'Meara of the Montreal Heart Institute, Montreal, QC, Canada. 

The goal of this team is to better understand the determinants of progression from risk factors to HF and death, and to test whether interventions at different stages can prevent progression and improve prognosis. HF is the end result of several complex processes that are only partially understood, with different phenotypic presentations and a range of comorbidities that affect survival and quality of life (QOL). This team focuses on three important but relatively neglected areas of HF research:

  1. HF phenotypes 

  2. Inflammation in HF

  3. Aging, comorbidity, and HF.

Team Leads

Dr. Philip Joseph
PHRI, McMaster University

Aim 1

HF phenotypes

 

The CHF Alliance supports existing cohorts and creates new collaborations to improve knowledge of HF phenotypes and make existing data more accessible.

Canadian Alliance for Healthy Hearts and Minds: CAHHM

The CAHHM is a prospective cohort study designed to examine the impact of the community-level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases in adults living in Canada. CAHHM has approximately 10,000 participants, including a First Nations cohort of approximately 1,300 individuals. It consists of a full characterization, including head and chest MRI, GWAS (being completed), and multiplex biomarker panel (partial). Dr. Sonia Anand (McMaster University, PHRI) is one of the Principal Investigators of the CAHHM and the CHF Alliance collaborator for this project.  

The CHF Alliance helps to repeat MRI in selected patient groups, complete the GWAS and biomarker panel, and supports the co-development of Indigenous co-identified priority projects to identify high-risk individuals for HF. The completion of the biomarker panel is well advanced in the Fisrt Nations cohort. Discussion are ongoing to repeat MRI in the First Nations cohort, and the follow-up study should begin in the middle of 2024. 

Canadian Cardiomyopathy Collaborative

Many separate cardiomyopathy datasets already exist across Canada. All of these contain many different and complementary data points that, taken together, would allow detailed phenotyping of patients with cardiomyopathy. However, there is currently no infrastructure in place to link all of these data to facilitate the development of large-scale studies and the use of artificial intelligence. Therefore, the CHF Alliance aims to provide the infrastructure to link these complementary datasets (clinical, biological, environmental, physiological) from cardiomyopathy patients across Canada available through the CHF Alliance, PRIMaCY (Precision Medicine in Cardiomyopathy International registry; over 2000 pediatric patients with hypertrophic cardiomyopathy), HiRO (Hearts in Rhythm Organization registry and biobank; over 5,700 participants) and others. This initiative will be carried out in collaboration with Dr. Seema Mital (SickKids), Dr. Rafik Tadros (Montreal Heart Institute) and Dr. Andrew Krahn (University of British Columbia). At this stage, REB and legal agreements have been initiated, 2300 eligible patients have been identified for a study of diastolic heart failure in cardiomiopathy, core platforms for genomics (SickKids), proteomics (PHRI), metabolomics (MHI), and imaging (SickKids, MHI and UBC) have been identified, and other cardiomyopathy patients have been identified from another registry, which is being explored for potential collaboration. This project is supported by Bristol Myers Squibb.  

In parallel to the Canadian Cardiomyopathy Collaborative, we are working closely with the Brain-Heart InterConnectome team and the Tannenbaum Open Science Institute (TOSI) to develop a cardiovascular Open Science platform. The TOSI platform, which works out of the Montreal Neurological Institute, is operational, focuses on neurological data, has particular expertise in imaging and genomics and has met the challenges of the ethical considerations involved with a database such as this. The Ottawa Heart Institute and the BHI have been working in collaboration with the TOSI to develop a sister platform that includes both cardiovascular and neurological data. The development of this platform is well advanced with a functional beta platform ready to test this fall in collaboration with the CHF Alliance. The goal is to include the maximum important cardiovascular databases in these open science platforms with the help of the CHF Alliance. Access to data is much facilitated but remains controlled and can only be granted according to patient consent and investigator approval. Various models for data analyses will be possible according to patient consents and investigator approval. These include a central data set that lends itself well for AI studies, and a distributed model that lends itself less well to AI studies but is good for more focused work. We believe that this Open Science initiative will become an important sustainable infrastructure for the national and international cardiovascular community.

On the other hand, analyses of existing databases is crucial to better understand HF phenotype and help with treatment decision, and that is what le following study aims for. 

Individualizing revascularization decisions in patients with heart failure and ischemic left ventricular dysfunction based on baseline surgical risk scores in the STICH and the REVIVEDBCIS-2 trials:

The primary cause of HF is the development of blockages in the arteries supplying blood to the heart. In the case of many blockages, bypass surgery helps patients live longer, although it is a major procedure. The use of heart catheters inserted through the wrist or the groin to go unblock the heart arteries with stents may represent a less invasive alternative to bypass surgery. The team will analyze the data from two large studies of patients with HF and multiple blockages to evaluate whether it is possible to use commonly used risk scores to identify which patients will live longer with a bypass surgery and with stents, and which patients will not. This way, it will allow the healthcare team to avoid offering these invasive procedures to patients who are unlikely to benefit from them, and to tailor therapy to those who will. The results of this study will help patients decide whether to undergo open-heart surgery, PCI, or neither procedure if they have HF and blockages in the arteries of their heart. The study is led by Dr. Guillaume Marquis-Gravel, a cardiologist at the Montreal Heart Institute, who received an Early Career Investigator Grant from the CHF Alliance to help conduct this study that will get started in September 2023.

Dr. Eileen O'Meara
Montreal Heart Institute

Translational team members

Dr. Salim Yusuf
PHRI, McMaster University

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Dr. Sonia Anand
PHRI, McMaster University

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Dr. Guillaume Marquis-Gravel
Montreal Heart Institute

Aim 2

Inflammation in HF

Inflammatory pathways are upregulated in some "cardio-inflammatory" HF subtypes and are associated with worse outcomes (1-3). Inhibition of inflammatory pathways (e.g. IL-1b) could improve HF-related outcomes (4). The efficacy of colchicine, a potent anti-inflammatory drug, will then be tested in two complementary HF trials.

1. The Reversing microvascular dysfunction in heart failure with ejection fraction >40% using colchicine study (Dr. Nadia Bouabdallaoui, Montreal Heart Institute) aims to gain a deeper understanding of how inflammation in the heart’s small blood vessels contributes to heart failure with preserved ejection fraction. The study will randomized 64 patients with Myocardial Flow Reserve (MFR) < 2.0 (marker of coronary microvascular dysfunction) and no evidence of ischemia at baseline to either low-dose colchicine (0.5 mg daily) or a matched placebo. Follow-up will occur at 6 months to assess the primary and secondary endpoints, which are respectively, the change from baseline to 6 months in MFR using PET imaging, and the change from baseline to 6 months in a broad set of circulating biomarkers of inflammation and remodeling using the Olink Multiplex inflammation panel. This study is partially funded by Heart and Stroke.

2. Colchicine and Thiamine in HF due to Ischemic Heart Disease (IHD): COLT-HF 

By inhibiting common inflammatory pathways that exacerbate HF and atherosclerotic progression, colchicine may reduce HF and ischemic cardiovascular outcomes in patients with HF and IHD (1, 2, 5, 6). In addition, thiamine is an essential cofactor in adenosine triphosphate (ATP) synthesis and cardiomyocyte energy metabolism; its deficiency is common in HF patients on chronic diuretic treatment (7-10). Thiamine supplementation may improve outcomes, but this hypothesis has not been tested in large randomized clinical trials (RCT)(8).

The team is conducting a 2x2 factorial RCT in 2,500 participants with HF secondary to IHD and left ventricular ejection fraction (LVEF) <45%. The first factorial randomizes participants to low-dose colchicine (0.5 mg daily) or placebo, while the second factorial is a prospective, randomized, open-label, blinded endpoint design with participants randomized to thiamine 300 mg daily or no thiamine. The composite of HF and ischemic cardiovascular outcomes will be evaluated over 3.5 years. The recruitment has started in one country and  the team is anticipating starting recruitment in the other 5 countries in the middle of 2024. This international study is led by Dr. Philip Joseph  (NCT05873881).

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Dr. Nadia Bouabdallaoui
Montreal Heart Institute

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Dr. Parminder Raina
McMaster University

Dr. Jorge Wong
PHRI, McMaster University

Ageing, comorbidity, and HF 

Bariatric surgery for the Reduction of cArdioVascular Events feasibility trial: BRAVE 

Obesity induces adverse cardiac (e.g., endothelial dysfunction, fibrosis, pericardial fat restriction) and systemic responses (e.g., plasma volume expansion, high mechanical load, inflammation, RAAS upregulation) that lead to HF (15-17). It is unclear whether weight loss in obese patients prevents HF (18-20). The team conducts a feasibility trial to test bariatric surgery versus best medical care in 200 severely obese participants (BMI > 35) with cardiovascular disease, including HF. The primary outcome is major cardiovascular events, including HF, at 5 years. This project is led by Drs. Salim Yusuf and Jorge Wong (McMaster University, PHRI). 

Recruitment is currently underway in Canada (6 sites). This study will lead to a large-scale randomized controlled trial to evaluate the efficacy of surgery in reducing cardiovascular complications in this study population (discussion are ongoing in other countries). 

Canadian Longitudinal Study on Aging: CLSA

The CLSA is a large, national, long-term study that is following approximately 50,000 individuals between the ages of 45 and 85 (at the time of recruitment) for at least 20 years (2033). Of these 50,000 individuals, approximately 30,000 come in for clinic follow-up every 3 years. The CLSA collects information on the changing biological, medical, psychological, social, lifestyle, and economic aspects of people's lives. These factors are studed to understand how, individually or in combination, they affect both the maintenance of health and the development of disease and disability as people age. Dr. Parminder Raina (McMaster University) is the lead principal investigator of CLSA. 

The CHF Alliance aims to add cardiac imaging (echocardiograms) to the 30,000 individuals who come to the clinic for follow-up to help diagnose of HF. This will be possible by training non-echocardiographers to obtain imaging and echo reports using artificial intelligence. Since the proposed project involves the use of artificial intelligence, we have initiated a collaboration with the team of Dr. Teresa Tsang (University of British Columbia, BC), experts in the development of algorithms for performing and reading echocardiograms using artificial intelligence. Dr. Tsang's team is responsible for training non-echocardiographers. Echocardiograms will be added at CLSA follow-up #4, beginning in the fall of 2024.

This project is strongly supported by the Fonds de Recherche du Québec - Santé which provided financial support for its implementation.

Dr. Andrew Krahn
University of British Columbia

Dr. Seema Mital
SickKids

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Dr. Rafik Tadros
Montreal Heart Institute

Aim 3

Translational sciences team members

Dr. Philip Joseph - Cardiologist, Associate Professor, McMaster University, PHRI (COLT-HF)

Dr. Salim Yusuf - Cardiologist, Professor, McMaster University, PHRI (BRAVE)

Dr. Jorge Wong - Cardiologist, Assistant Professor, McMaster University, PHRI (BRAVE)

Dr. Jean Rouleau - Cardiologist, Professor, Montreal Heart Institute, Université de Montréal 

Dr. Eric Wong - Clinical Scholar and PhD Candidate, University of Toronto (COLT-HF)

Dr. Eileen O'Meara - Cardiologist, Associate Professor, Montreal Heart Institute, Université de Montréal

Dr. Nadia Bouabdallaoui - Cardiologist, Clinical Assistant Professor, Montreal Heart Institute, Université de Montréal (COLpEF)

Dr. Guillaume Marquis-Gravel - Cardiologist, Clinical Assistant Professor, Montreal Heart Institute, Université de Montréal (STICH)

Dr. Sonia Anand - Vascular Medicine Specialist, Professor, McMaster University, PHRI (CAHHM)

Dipika Desai - Program Manager, McMaster University, PHRI (CAHHM)

Dr. Matthias Friedrich - Cardiologist, Professor, McGill University Health Centre (CAHHM)

Dr. Judy Luu - Women's Heart Health Cardiologist, Assistant Professor, McGill University Health Centre (CAHHM)

Dr. Doug Lee - Cardiologist, Professor, Peter Munk Cardiac Center of University Health Network, University of Toronto (CAHHM) 

Dr. Paul Poirier - Cardiologist, Professor, Quebec Lung and Heart Institute, Université Laval (CAHHM)

Dr. Marie-Ève Piché - Cardiologist, Assistant Professor, Quebec Lung and Heart Institute, Université Laval (CAHHM)

Dr. Peter Liu - Cardiologist, Professor, University of Ottawa Heart Institute, University of Ottawa (CAHHM, Open Science Initiative)

David Nichol - Project Manager, Brain-Heart Interconnectome, University of Ottawa Heart Institute (CAHHM, Open Science Initiative)

Dr. Parminder Raina - Professor, McMaster University (CLSA)

Dr. Teresa Tsang - Cardiologist, Professor, Vancouver General Hospital, UBC Hospital, University of British Columbia (CLSA, CCC) 

Dr. Darwin Yeung - Cardiologist, Clinical Assistant Professor, Vancouver General Hospital, UBC Hospital, University of British Columbia (CLSA)

Dr. Christina Luong - Cardiologist, Clinical Assistant Professor, Vancouver General Hospital, University of British Columbia (CLSA)

Dr. Michael Tsang - Cardiologist, Clinical Assistant Professor, Vancouver General Hospital, University of British Columbia (CLSA)

Dr. John Jue - Cardiologist, Clinical Associate Professor, Vancouver General Hospital, University of British Columbia (CLSA)

Dr. Kenneth Gin - Cardiologist, Professor, Vancouver General Hospital, University of British Columbia (CLSA) 

Dr. Parvathy Nair - Cardiologist, Clinical Assistant Professor, Vancouver General Hospital, University of British Columbia (CLSA)

Dr. Jeff Yim - Cardiology Resident, University of British Columbia (CLSA) 

Dr. Inchang Hwang - Post-Doctoral Fellow, Vancouver General Hospital, University of British Columbia (CLSA)

Ruta Masiuliene - Trainee, University of British Columbia (CLSA)

Dr. Seema MitalCardiologist, Professor, The Hospital for Sick Children, University of Toronto (CCC)

Dr. Rafik TadrosCardiologist, Montreal Heart Institute, Université de Montréal (CCC)

Dr. Andrew Krahn - Cardiologist, Professor, University of British Columbia (CCC)

Raj Akilen - Project Manager, The Hospital for Sick Children (CCC)

Brianna Davies - Research Genetics Counsellor, University of British Columbia (CCC)

Michael Harvey - Patient Partner, New-Foundland and Labrador (CCC)

Dr. Julia Cadrin-Tourigny - Cardiologist, Assistant Professor, Montreal Heart Institute, Université de Montréal (CCC)

Dr. Maxime Tremblay-Gravel - Cardiologist, Clinical Assistant Professor, Montreal Heart Institute, Université de Montréal (CCC)

Dr. Jacinthe Boulet - Cardiologist, Assistant Professor, Montreal Heart Institute, Université de Montréal (Open Science Initiative, CCC)

Dr. Phyllis Billia - Cardiologist, Assistant Professor, University Health Network, University of Toronto (Open Science Initiative)

Dr. Matthieu Ruiz - Scientist, Assistant Professor, Montreal Heart Institute, Université de Montréal (CCC)

Dr. Guillaume Paré - Medical Biochemist, Professor, PHRI, McMaster University (CCC)

Dr. Mark Friedberg - Cardiologist, Professor, The Hospital for Sick Children, University of Toronto (CCC)

Dr. Luc Mertens - Section Head Echocardiography, Cardiologist, Professor,  The Hospital for Sick Children, University of Toronto (CCC)

Dr. Robert Avram - Cardiologist, Clinical Assistant Professor, Montreal Heart Institute, Université de Montréal (CCC)

Dr. Abhinav Sharma - Cardiologist, Assistant Professor, McGill University Health Centre, McGill University (CCC)

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