Heart Failure Innovation Cluster

The incidence and prevalence of heart failure (HF) is on the increase, remains one of the most common reasons for admission to hospital, and is associated with significant morbidity and mortality. HF occurs due to depressed contractile and/or relaxation properties of the myocardium and there is no cure. Heart failure with preserved ejection fraction (HFpEF) and right HF are two common forms of the disease that are in focus here. Further, abnormal cardiac growth and remodelling is a hall mark of all HF and mechanisms which contribute are under investigation. The research cluster, composed of clinicians, scientists and population health experts using a wide array of inter-disciplinary approaches, is engaged in generating knowledge to better understand, manage, prevent and treat HF.

Goals of the Cluster

The Innovation Cluster participants are addressing major gaps in the knowledge base for heart failure including:

Translational Research:

  • Development of biomarkers to risk stratify and detect early stages of HF and cardiac dysfunction to address the problem that the disease presents too late. 
  • Innovative mechanisms controlling cardiac remodelling in terms of cell growth, death and differentiation in response to stress (inflammation, metabolic, chemical and blood pressure). Both transcriptional and post-transcriptional mechanisms in the stress induced hypertrophic response are being evaluated. 
  • The improvement of heart functions via cardiac regeneration using stem cells and biomaterials as well as state of the art imaging/surgical/medical devices. 

Clinical and Health Systems Research:

  • Pathophysiology and disease classification of diastolic heart failure (HFpEF), a major diagnostic and therapeutic conundrum as well as treatment/preventative measures.
  • Mechanisms of right HF, including pulmonary hypertension, representing a difficult group of very sick patients with limited options and understanding of pathophysiology.
  • Personal tailored triage, risk profiling, stratified treatment, discharge planning, follow up. 
  • Best systems-based innovations to avoid re-hospitalisation. 
  • Global heart failure epidemiology. 
  • Primary care collaborations e.g. automated EMR screening of patients at a high risk of HF; role of BNP testing in the diagnosis of HF with preserved ejection fraction in primary care settings. 

Innovation Cluster Scientists

Lead: Lisa Mielniczuk, MD, University of Ottawa Heart Institute
Co-lead: Balwant Tuana, PhD, University of Ottawa and University of Ottawa Heart Institute

Team members at the University of Ottawa Heart Institute:
Rob Beanlands, MD, David Birnie, MD, Patrick Burgon, PhD, Sharon Chih, MD, Thais Coutinho, MD, Ross Davies, MD, Darryl Davis, MD, Rob deKemp, PhD, Alexandre Dick, MD, Girish Dwivedi, MD, Haissam Haddad, MD, Peter Liu, MD, Marc Ruel, MD, Heather Sherrard, BScN, MHA, Ellamae Stadnick, MD, Alexandre Stewart, PhD, Erik Suuronen, PhD, John Veinot, MD. 

Other Team members: 
George Chandy, MD, Physician, Respirology, TOH
Carole Dennie, MD, Cardiologist, Radiology, TOH
Susan Dent, MD, Physician, Medical Oncology, TOH
Pasan Fernando, PhD, Assistant Professor, Faculty of Medicine, University of Ottawa
Christopher Johnson, MD, Cardiologist, The Ottawa Hospital
Angeline Law, MD, Cardiologist, The Ottawa Hospital
Lynn Megeney, PhD, Senior Scientist, Regenerative Medicine, OHRI
Mona Nemer, PhD, Vice President Research, University of Ottawa
Elena Pena Fernandez, MD, Assistant Professor Radiology and Cardiothoracic Radiologist, University of Ottawa
William Stanford, PhD, Senior Scientist, Sprott Centre for Stem Cell Research, OHRI
Duncan Stewart, MD, CEO & Scientific Director, OHRI
Rebecca Thornhill, PhD, Diagnostic Imaging, Clinical Investigator, TOH

Ongoing Pilot Projects
  1. Elucidating the Mechanisms of Right Heart Failure

    Project led by Lisa Mielniczuk, MD, Susan Dent, MD and Duncan Stewart, MD.

    The overall theme to this project is the evaluation of the mechanisms and contributors to right heart failure (HF). The team is evaluating the role of pulmonary hypertension and lung metabolism and chemotherapeutic agents as they relate to the development of right heart failure in cardiovascular disease.

  2. Implanting Novel Biomaterials in Cardiac Hibernating and Scar Tissue of Surgical Patients with Heart Failure
  3. Frailty Assessment in Advanced Heart Failure and the Impact of Intensive Cardiac Rehabilitation
  4. Characterization of Lung Parenchymal and Vascular Abnormalities, using Cardiac Magnetic Resonance Imaging and Dual Source Computed Tomography and Correlation with Metabolism in Pulmonary Vascular Remodeling associated with HFpeF and right heart failure. 
  5. Assessment of Ventricular Systolic Interdependence as a Prognostic Variable in Progressive Right Ventricular Failure.
Selected Innovation Cluster Publications
  1. Ahmadi A, L Thorn S, Alarcon EI, Kordos M, Padavan DT, Hadizad T, Cron GO, Beanlands RS, DaSilva JN, Ruel M, deKemp RA, Suuronen EJ. PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarctionBiomaterials. 2015 May;49:18-26. 
  2. Ahmadi A, Ohira H, Mielniczuk LM. FDG PET imaging for identifying pulmonary hypertension and right heart failureCurr Cardiol Rep. 2015 Jan;17(1):555. 
  3. Mayfield A, Tilokee EL, McNeil B, Lam BK, Ruel M, Suuronen EJ, Courtman DW, Stewart DJ, Davis DR, The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac functionBiomaterials. 35(1):133-42, 2014. 
  4. Hall AB, Ziadi MC, Leech J, Chen S-Y, Burwash I, Renaud J, deKemp R, Haddad H, Mielniczuk L, Yoshinaga K, DaSilva J, Walter O, Guo A, Chen L, Garrard L, Floras J, Beanlands RB. Effects of Short-Term Continuous Positive Airway Pressure on Myocardial Sympathetic Nerve Function and Energetics in Patients with Heart Failure and Obstructive Sleep ApneaCirculation. 2014 Sep 9;130(11):892-901.
  5. Almontashiri NA, Chen HH, Mailloux RJ, Tatsuta T, Teng AC, Mahmoud AB, Ho T, Stewart NA, Rippstein P, Harper ME, Roberts R, Willenborg C, Erdmann J; CARDIoGRAM Consortium, Pastore A, McBride HM, Langer T, Stewart AF. SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS, and is associated with multiple clinical phenotypesCell Rep. 2014 May 8;7(3):834-47.
  6. Zhang L, Chen X, Sharma P, Moon M, Sheftel AD, Dawood F, Nghiem MP, Wu J, Li RK, Gramolini AO, Sorensen PH, Penninger JM, Brumell JH, Liu PP. HACE1-dependent protein degradation provides cardiac protection in response to haemodynamic stressNat Commun. 2014 Mar 11;5:3430.
  7. Robillard J, Pena E, Veinot J, Fullop J, Dennie C. Pericardial Lymphangiohemangioma: Multimodality imaging features and pathological correlation. Circulation. 2014 Jun 24;129(25):e657-9. 
  8. Putinski C, Abdul-Ghani M, Stiles R, Brunette S, Dick SA, Fernando P, Megeney LA. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophyProc Natl Acad Sci U S A. 2013 Oct 22;110(43):E4079-87.
  9. Coutinho T, Goel K, Corrêa de Sá D, Carter RE, Hodge DO, Kragelund C, Kanaya AM, Zeller M, Park JS, Kober L, Torp-Pedersen C, Cottin Y, Lorgis L, Lee SH, Kim YJ, Thomas R, Roger VL, Somers VK, Lopez-Jimenez F. Combining body mass index with measures of central obesity in the assessment of mortality in subjects with coronary disease: role of “normal weight central obesity”J Am Coll Cardiol. 2013 Feb 5;61(5):553-60.
  10. Dent S, Oyan B, Honig A, Mano M, Howell S. HER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trialsCancer Treat Rev. 2013. 
  11. Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, Simpson CS, Ayala-Paredes F, Coutu B, Leiria TL, Essebag V. BRUISE CONTROL Investigators. Pacemaker or defibrillator surgery without interruption of anticoagulationN Engl J Med. 2013 May 30;368(22):2084-93.
  12. Valaperti A, Nishii M, Liu Y, Naito K, Chan M, Zhang L, Skurk C, Schultheiss HP, Wells GA, Eriksson U, Liu P P (2013). Innate immune interleukin-1 receptor-associated kinase 4 exacerbates viral myocarditis by reducing CCR5(+) CD11b(+) monocyte migration and impairing interferon productionCirculation, 128(14), 1542-1554.
  13. Westendorp B, Major JL, Nader M, Salih M, Leenen FH, Tuana BS. The E2F6 repressor activates gene expression in myocardium resulting in dilated cardiomyopathyFASEB J. 2012 Jun;26(6):2569-79
Funding

Researchers in the Innovation Cluster are supported by peer review funds from the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada (HSFC), Canadian Diabetes Association, Genome Canada and the Natural Sciences and Engineering Council of Canada (NSERC). 

 

 

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