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The Translational Science 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 will help to repeat MRI in selected patient groups, complete the GWAS and biomarker panel, and support the co-development of Indigenous co-identified priority projects to identify high-risk individuals for HF.  

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).

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. Colchicine trial in HFpEF: COLpEF

This study, led by Dr. Nadia Bouabdallaoui (Montreal Heart Institute), is in the organizational phase. It will assess the impact of colchicine vs placebo in patients with HF, a left ventricular ejection fraction >45% and diabetes or obesity or elevated inflammatory biomarkers. This study is funded by the Heart and Stroke Foundation.

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 will then conduct a 2x2 factorial RCT in 2,500 participants with HF secondary to IHD and left ventricular ejection fraction (LVEF) <45%. The first factorial will randomize participants to low-dose colchicine (0.5 mg daily) or placebo, while the second factorial will be 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 study is led by Dr. Philip Joseph and enrollment is expected to begin in summer 2023 (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 60 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. This study may lead to a large-scale randomized controlled trial to evaluate the efficacy of surgery in reducing cardiovascular complications in this study population.

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. 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

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.

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