At this year’s premier international gathering for heart disease, the American Heart Association Scientific Sessions, sharing expertise was a major aspect of the University of Ottawa Heart Institute’s presence. In Ask the Expert and seminar sessions, surgeons Marc Ruel, Munir Boodhwani, David Glineur and Vincent Chan spoke on a variety of topics, including aspects of surgical training, the impact of diabetes, bypass grafts, and gender differences in the outcomes for mitral valve repair.
Cardiologists Rob Beanlands, Thais Coutinho, Lisa Mielniczuk and Benjamin Chow spoke on inflammatory cardiomyopathy, gender differences in arterial function, heart failure imaging, and the role of cardiac computed tomography (CT). Scientist Erik Suuronen, PhD, spoke on tissue engineering and electrophysiology nurse Krystina Lewis spoke on shared decision making in cardiovascular care.
Scientific presentations covered a wide range of basic and clinical research. Representative studies from each branch are profiled below.
Factors Impacting the Effectiveness of Stem Cell Therapy
Regenerative medicine—harnessing the body’s own stem cells to repair damaged heart tissue—holds the promise of actually restoring some of the heart’s function after a heart attack. The Cardiac Translational Research Laboratory of Darryl Davis, MD, an electrophysiologist and researcher at the Heart Institute, presented three studies at the AHA conference that looked at factors affecting how well donor cardiac stem cells do their job.
Two of the studies looked at what happens to cardiac stem cells as the body ages or is battered by illness. In one, the researchers tested whether advanced donor age or damage from ischemic cardiomyopathy (dilated and weakened heart muscle due to a heart attack) affect regenerative ability. They collected and cultured heart tissue samples from young and old mice that were either healthy or had experienced an induced heart attack. The resulting explant-derived cardiac stem cells (EDCs) were then tested for their potential repair capabilities. While donor age alone made no real difference, cells from older donors with ischemic cardiomyopathy had less propensity to form new heart cells, produced fewer molecular signals that promote healing, and were less resistant to cell death than cells from younger donors with the condition.
In another study, the researchers cultured EDCs from heart tissue routinely removed from people during cardiac surgery. The researchers then compared the repair abilities of EDCs cultured from people with few other health problems with those cultured from people with extensive health problems. They found that the stem cells’ ability to repair heart tissue in mice declined with accumulated health problems in the donors and that this effect was associated with a decrease in production of cell-signaling molecules that promote repair.
The third study looked at the extent to which physical incorporation and persistence of transplanted cells in the heart contributes to the benefits of cardiac stem cell therapy. The researchers treated mice with cardiac stem cells cultured from human tissue. One week after the mice received the stem cells, the researchers injected half with a compound to destroy the donor cells. Mouse hearts that only had exposure to functional cardiac stem cells for a week showed a decline in measures of heart function and damage compared with those in which the donor cells were allowed to persist, showing the regenerative benefit of long-term exposure.
Anti-Clotting Drug Improves Myocardial Blood Flow
For patients with acute coronary syndrome, treatment with the anti-clotting drug ticagrelor has been shown to reduce the risk of death compared to treatment with clopidogrel, but the reasons for this reduced risk have not been clear.
A study led by Heart Institute nuclear imaging resident Matthieu Pelletier-Galarneau, MD, working under Terrence Ruddy, MD, tested the relative abilities of ticagrelor and clopidogrel to improve myocardial blood flow (MBF). In a small trial, 22 patients were randomly assigned to receive either 10 days of ticagrelor followed 10 days of clopidrogrel or vice-versa; both regimens included at least five days of rest between the two drugs. MBF during active medication use was measured by positron emission tomography (PET) scanning with the heart at rest and under stress by two different doses (intermediate and high) of the drug adenosine.
Global MBF was significantly greater under stress with ticagrelor than clopidogrel at high doses of adenosine, but no differences were seen at rest or with intermediate doses. For segments of the heart with low MBF reserve, MBF was significantly greater with ticagrelor at both intermediate and high doses of adenosine but not at rest. For segments with high MBF reserve, MBF was significantly greater with ticagrelor at rest and with intermediate doses of adenosine. The researchers suggest that the improved MBF seen under stress with ticagrelor administration may help explain the reduced risk of death as compared with clopidogrel.