Toronto researchers to use new AI, stem cell approaches to address heart failure

As the world marks international Heart Month, the Ted Rogers Centre for Heart Research today announces its first-ever $1 million innovation grants, awarded to world-first projects positioned to alleviate the massive burden of heart failure on patients, loved ones and health-care systems.

“Our Centre is uniquely positioned to invest in emerging technology that delivers new diagnostic and therapeutic approaches to heart failure,” said Dr. Mansoor Husain, executive director, Ted Rogers Centre for Heart Research. “To support our mission of addressing heart failure across the lifespan, we funded a pair of visionary projects that require a generous level of support that most granting agencies aren’t able to provide.”

The two projects mark significant steps forward in advancing solutions for an endemic disease that in Canada affects at least one million people and costs the health-care system over $3 billion each year:

How AI can keep patients out of hospital

1. Douglas Lee, Ted Rogers Chair in Heart Function Outcomes, will lead the first funded project, which will create a new machine learning model to predict prognoses of patients with heart failure, preventing unnecessary admissions to hospital.

Heart failure is a leading cause of hospital readmissions that bear a substantial burden on the health-care system of most countries. In general, the disease is treated reactively: a patient experiences symptoms, heads to the emergency department, and is admitted to hospital.

“We have hit a wall in predicting readmissions using traditional clinical methods,” said Dr. Lee. “As it stands, without the right tools in place, low-risk patients may be unnecessarily admitted while high-risk patients could be inadvertently discharged home.”

To better predict outcomes and improve care, the team will develop a new algorithm based on an array of information that includes biomarkers, physiologic data, blood samples, and a patient’s own reported symptoms. This will be combined with evolving technology such as remote patient monitoring and machine learning. Together, the aim is to develop a complete, integrated model to predict heart failure readmissions.

This project substantially builds on Dr. Lee’s groundbreaking EHMRG algorithm.

Co-investigators: Dr. Heather Ross (UHN), Prof. Anthony Gramolini (U of T), Dr. Patrick Lawler (UHN), Dr. Slava Epelman (UHN), Jane MacIver (UHN), Prof. Catherine Kreatsoulas (Harvard / U of T), and Prof. Anna Goldenberg (SickKids).

Team members: Dr. Daniel Levy (Framingham Heart Study), Dr. Jennifer Ho (Massachusetts General Hospital), Dr. Faiez Zannad (HOMAGE study, France), Prof. Peter Austin (ICES), Prof. Cedric Manlhiot (SickKids), Dr. Geoffrey Anderson (U of T), Prof. Emily Seto (U of T), DrDinesh Thavendiranathan (UHN), Dr. Richard Tsang (UHN), Dr. Paul Angaran (UHN), Dr. Anna Woo (UHN), Dr. Phyllis Billia (UHN), Dr. Louise Sun (Ottawa Heart Institute), Dr. Peter Liu (Ottawa Heart Institute), Dr. Carolina Alba (UHN), Dr. Josef Stehlik (University of Utah), Dr. Valeria Rac (UHN).

Bioengineering to target cardiomyopathy

James Ellis, senior scientist at SickKids, leads the second funded project, which will use stem cells and bioengineered tissues to test new treatments for patients affected by mutations that cause heart disease.

Cardiomyopathy is a genetic condition that either thins and weakens or thickens and stiffens the heart muscle. It is the most common cause of heart failure and sudden cardiac death in children. There are no effective treatments today.

This innovative project combines stem cells, bioengineered tissues and genomics to study if drugs that target myosin – the protein that causes a heart to contract – are effective in children and adults with cardiomyopathy. At the same time, they will see if a patient’s genotype can predict response to therapy.

Researchers will leverage new reprogramming and gene-editing technology to create models of disease in which drugs can be studied. To do so, they will take skin or blood cells from patients, reprogram them into stem cells, and convert them into heart cells. If they discover that a drug works best in patients with certain gene defects but not others, it will lay the groundwork for precision medicine in cardiomyopathy.

“We hope that evidence-based use of these medicines will eventually reduce heart failure in these patients and will prolong their lives,” said Prof. Ellis.

Co-investigators: Dr. Seema Mital (SickKids), Prof. Craig Simmons (U of T), Prof. Milica Radisic (U of T), and Dr. Phyllis Billia (UHN).