Linked by the heart
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:
Team Leads
Dr. Philip Joseph
PHRI, McMaster University
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. At this stage, the team is recontacting participants with the goal for inviting 2100 participants from Ontario, Quebec and British-Columbia for a repeat assessment at clinical sites, as well as repeat MRI, and a more detailed on-line cognitive assessment (450 participants have already completed their MRI). The completion of the biomarker panel is well advanced in the Fisrt Nations cohort, with 583 samples analyzed. Discussion are ongoing to repeat MRI in the First Nations cohort.
​
Click here to learn more about CAHHM and how to access data.
​
Canadian Cardiomyopathy Collaborative (C3)
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). This collaborative helped expand the AID-HF (AI model for diastolic HF) project nationally bringing together the largest cohorts of cardiomyopathy across Canada and across the lifespan. At this stage, REB was obtained and data transfer agreements were executed. The Montreal Heart Institute (MHI, Dr. Ruiz) serves as the metabolomics core lab, the Population Health Research Institute (PHRI, Dr. Paré) serves as the proteomics core lab, and SickKids as the imaging core lab. The C3 has completed phenotyping of its discovery cohort of 780 participants obtained from the Heart Centre Biobank (336), Hearts in Rhythm Organization (134) and HiRO-HCM (310). Biological samples available from this cohort were submitted to labs for genome sequencing (750), lipidomics and proteomics (466). All biological data is expected in May 2026, after which analysis will begin. This project is supported by Bristol Myers Squibb, the Ted Rogers Centre for Heart Research and the CHF Alliance.
​
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. This health platform named ARCHIMEDES (Advanced Research Collaboration for Health Integration, Medical Exploration, and Data Synthesis) aims to deliver a multimodal informatics infrastructure to provide users access to curated and federated brain-heart health data, with open-access repository and advanced predictive analytics functionality. Users of ARCHIMEDES can collect, manage, share, access, aggregate, and analyze data. With ARCHIMEDES, data access is as open as possible and as restrictive as necessary, meaning that data can be publicly and freely available without any conditions of use, available to specified users as indicated by the PI, or available on a case-by-case basis upon request to the original data provider. The ARCHIMEDES team, co-led by Dr. Jody Edwards and Dr. Kelly Cobey (both UOHI) developed 4 different data sharing consent templates (sharing de-identified data openly, sharing de-identified data restricted access, obtaining retrospective consent for open sharing, obtaining retrospective consent for restricted access sharing) and has data standardization projects underway. At this stage, ARCHIMEDES is active, meaning researchers can access data with the appropriate authorization depending on the data accessibility (open or controlled), and they can create accounts for data contribution (requires a Data Contribution Agreement at an institutional level, signed by the institutional Signing Official). The ARCHIMEDES website is live and many resources, such as consent templates, data comprehensive standards, data de-identification toolkits and demographic forms, have been made available to researchers.
​
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 analyzed 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. The goal is to 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 team found that the treatment effect of Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Grafting (CABG) over optimal medical therapy was not modified by baseline surgical risk. Patients in the REVIVED-BCIS2 trial were at higher baseline surgical risk compared with patients from the STICH trial and may not have been deemed appropriate surgical candidates. Whether PCI would reduce all-cause mortality in a lower-risk population remains unknown. 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
Dr. Sonia Anand
PHRI, McMaster University
Dr. Guillaume Marquis-Gravel
Montreal Heart Institute
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, Centre Hospitalier de l'Université de Montréal) 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. The study has been delayed since the Principal Investigator moved to a new Research Center. However, although recruitment has not yet started, the team successfully established the required research infrastructure and interdisciplinary collaborations, positioning the study for recruitment initiation within the institution. 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 is ongoing in five countries (56 sites), and the team. To date, approximately 900 participants have been recruited. The team is hoping to complete recruitment in mid 2027. This international study is led by Dr. Philip Joseph (NCT05873881).
Dr. Nadia Bouabdallaoui
Montreal Heart Institute
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).
The vanguard phase is completed and the team is now working on the larger scale study that will enroll approximately 700 participants in 6 different countries (currently enrolling in 19 sites). To date, 219 participants have been enrolled in the study. The primary outcomes would be the feasibility and major CV events, including HF, changes in weight, quality of life and NYHA at 5 years. This trial will determine whether weight loss in obese individuals can reduce the development of HF progression.
​
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. Addition of echocardiograms started with follow-up #4. To date, more than 8,000 images have been collected.
This project is strongly supported by the Fonds de Recherche du Québec - Santé which provided financial support for its implementation.
​
Click here to learn more about CLSA and how to access data.
Dr. Andrew Krahn
University of British Columbia
Dr. Seema Mital
SickKids
Dr. Rafik Tadros
Montreal Heart Institute
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 Mital - Cardiologist, Professor, The Hospital for Sick Children, University of Toronto (CCC)
Dr. Rafik Tadros - Cardiologist, 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)
References
1. Adamo L, Rocha-Resende C, Prabhu SD and coll. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol 2020;17:269–285.
2. Murphy SP, Kakkar R, McCarthy CP and coll. Inflammation in Heart Failure: JACC State-of-theArt Review. J Am Coll Cardiol 2020;75:1324–1340.
3. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013;62:263–271.
4. Everett BM, Cornel JH, Lainscak M and coll. Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation 2019;139:1289–1299.
5. Segiet OA, Piecuch A, Mielanczyk L and coll. Role of interleukins in heart failure with reduced ejection fraction. Anatol J Cardiol 2019;22:287–299.
6. Libby P. Targeting Inflammatory Pathways in Cardiovascular Disease: The Inflammasome, Interleukin-1, Interleukin-6 and Beyond. Cells 2021;10:951.
7. DiNicolantonio JJ, Niazi AK, Lavie CJ and coll. Thiamine supplementation for the treatment of heart failure: a review of the literature. Congest Heart Fail 2013;19:214–222.
8. Shimon I, Almog S, Vered Z and coll. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med 1995;98:485–490.
9. Teigen LM, Twernbold DD, Miller WL. Prevalence of thiamine deficiency in a stable heart failure outpatient cohort on standard loop diuretic therapy. Clin Nutr 2016;35:1323–1327.
10. Wong EKC, Lee JY, Leong DP and coll. Thiamine versus placebo in older heart failure patients: study protocol for a randomized controlled crossover feasibility trial (THIAMINE-HF). Pilot Feasibility Stud 2018;4:149.
11. Tersalvi G, Gasperetti A, Schiavone M and coll. Acute heart failure in elderly patients: a review of invasive and noninvasive management. J Geriatr Cardiol 2021;18:560–576.
12. Butrous H, Hummel SL. Heart Failure in Older Adults. Can J Cardiol 2016;32:1140–1147.
13. Malkin CJ, Pugh PJ, West JN and coll. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J 2006;27:57–64.
14. Toma M, McAlister FA, Coglianese EE and coll. Testosterone supplementation in heart failure: a meta-analysis. Circ Heart Fail 2012;5:315– 321.
15. Sabbah MS, Fayyaz AU, Denus S de and coll. Obese-Inflammatory Phenotypes in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail 2020;13:e006414.
16. Packer M, Kitzman DW. Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2. JACC Heart Fail 2018;6:633–639.
17. Savji N, Meijers WC, Bartz TM and coll. The Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF. JACC Heart Fail 2018;6:701–709.
18. Sundström J, Bruze G, Ottosson J and coll. Weight Loss and Heart Failure: A Nationwide Study of Gastric Bypass Surgery Versus Intensive Lifestyle Treatment. Circulation 2017;135:1577–1585.
19. Brathwaite BM, Howell RS, Petrone P and coll. Safety of Bariatric Surgery in Patients With Congestive Heart Failure: Results of an 11-Year Retrospective Study. Am Surg 2021;3134821991975.
20. Vest AR. Has the Time Come to Be More Aggressive With Bariatric Surgery in Obese Patients With Chronic Systolic Heart Failure? Curr Heart Fail Rep 2018;15:171–180.
21. Celano CM, Villegas AC, Albanese AM and coll. Depression and Anxiety in Heart Failure: A Review. Harv Rev Psychiatry 2018;26:175–184.
22. Alemoush RA, Al-Dweik G, AbuRuz ME. The effect of persistent anxiety and depressive symptoms on quality of life among patients with heart failure. Appl Nurs Res 2021;62:151503.
23. Rutledge T, Reis VA, Linke SE and coll. Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol 2006;48:1527–1537.