Hamilton Health Sciences
Pilot Projects
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2010: CANNeCTIN Projects Funded 

RIVAL - Sanjit Jolly (McMaster University) and Shamir Mehta (McMaster University); $79,146; Strategic Investment

In patients with Acute Coronary Syndromes (ACS) major bleeding is a common complication of antithrombotic therapies and invasive procedures and increases the risk of death and ischemic events 2 to 4 fold. Several randomized trials (OASIS and HORIZONS) have demonstrated that a reduction in early bleeding events using safer antithrombotic therapies is strongly associated with a reduction in longer term mortality, MI and stroke, and this relationship is likely to be causal. A substantial proportion of major bleeding events in patients with ACS are caused directly by puncture of the femoral artery used for cardiac catheterization.  These events can potentially be eliminated by the less invasive approach of using radial artery access, a more superficial and easily compressible site. Our meta-analysis of 18 small randomized trials (n=4458 patients, 61 major bleeding events), showed radial compared with femoral access was associated with a 73% reduction in major bleeding (0.5% vs. 2.3%, respectively; OR 0.27, 95% CI 0.16-0.45, p<0.001) and a trend toward reduction in death, MI or stroke (2.5% vs. 3.8%; OR 0.71, 95% CI 0.49-1.01, p=0.058). However, most interventional cardiologists do not view the data from small randomized trials as definitive and have been reluctant to adopt the radial artery approach. Further, current practice guidelines do not recommend a specific access site (i.e. radial vs. femoral) due to the lack of large adequately powered trials comparing both efficacy and safety of the two approaches. Our hypothesis is that radial compared to femoral access will reduce death, MI and stroke events by reducing major bleeds. We have currently recruited 5800 patients and the planned sample size of 7000 patients will ensure an 80% power to detect a 27% RRR in the primary outcome. If radial access is proven to definitively reduce major bleeding, and reduce death, MI and stroke, practice guidelines will change to recommend radial access as the preferred access site for coronary intervention and tens of thousands of major bleeding and ischemic events will be prevented each year worldwide.

VELETI II - Josep Rodés-Cabau (Institut Universitaire de Cardiologie et de Pneumologie de Québec); $107,000; Strategic Investment

The VELETI II trial will provide new information regarding the impact of stenting coronary saphenous vein-coronary graft moderate non-obstructive stenosis on coronary events and on the fate of the coronary vein graft stenosis and stent. There is good evidence that coronary saphenous vein graft (SVG) with a 30 to 60% stenosis is a predictor of graft occlusion and coronary events. In our center, we have confirmed these observations and subsequently did the first randomized controlled trial (the VELETI trial) in 57 patients measuring with angiography and ultrasound the venous graft stenosis at entry and one year later; in this study, 30 patients were randomized to stenting of SVG and optimal medical treatment and 27 to optimal medical treatment. We showed that stenting prevented the progression of atherosclerosis compared to the control group. There was also a trend in the stented group to a lower event rate, the composite of cardiovascular death, acute coronary syndrome and revascularization. However, the VELETI trial was a single center study carried out in a highly motivated institution with a lot of experience in the treatment of SVGs. Also, it was the very first plaque sealing trial ever done and the primary outcome was based on intravascular ultrasound measurements, with clinical outcomes as secondary endpoints. We intend to do a multicenter pilot study targeted on clinical outcomes and graft permeability involving 10 to 15 Canadian centers to test the feasibility and safety of such a SVG plaque sealing strategy in a larger-scale scenario.

Global Regsitry of Rheumatic Heart Disease (RHD) - Dr. Ganesan Karthikeyan (New Delhi) and the CANNeCTIN Rheumatic Heart Disease Working Group

Rheumatic heart disease (RHD) is the principal cause of valvular heart disease related mortality and morbidity worldwide, predominantly affecting children and young adults. Not only does RHD lead to over 200,000 deaths annually, it also adversely affects quality of life, productivity and income. Although the burden of disease is largely confined to low and middle-income countries, there is likely a migration-associated increase in the number of cases in developed countries. Despite the profound global burden, there are no contemporary data documenting the presentation, clinical course, complications and practice patterns that exist throughout the world. As such, this has limited the development of consensus guidelines regarding prevention and management strategies for RHD. This registry proposes to prospectively evaluate, and compare the demographics, clinical presentation, practice patterns and clinical outcomes of rheumatic heart valve disease in low and middle income countries. In its pilot phase this registry is designed as a prospective, international, multi-center registry of 3000 RHD patients recruited from centers in India, South Africa and several other participating countries from Africa. In addition to documenting region specific differences in clinical and practice patterns, we will record key outcome events, including death, stroke, heart failure, and major bleeding, over a 2-year period. This pilot study will set the stage for a larger and more comprehensive study involving other low and middle income countries and some high income countries. To our knowledge, this is the first attempt to formally compare patient and practice profiles of rheumatic valvular disease in developing countries. We believe that the insights gained from this global effort will help identify strategies to prevent and manage RHD, and its complications.

Prevention of Arrhythmia Device Infection Trial: Cluster Crossover (PADIT Cluster Crossover) - Dr. Andrew Krahn (University of Western Ontario); $58,800 (plus PHRI study coordination support); Arrhythmia Working Group

This is a prospective randomized cluster crossover pilot study to prevent infection in high-risk patients undergoing an arrhythmia device procedure. This will involve 350 patients undergoing a second procedure on an arrhythmia device pocket (generator or lead replacement, pocket or lead revision, upgrade) in 3 centers. Centers will be randomized to a 3-month period of conventional vs. aggressive prevention of infection. After 3 months, a wash out period of 1 month will take place, followed by cross over to the alternate strategy. Conservative therapy is a single dose of preoperative intravenous antibiotics compared to aggressive therapy with preoperative intravenous antibiotics, intracavitary antibiotics and postoperative oral antibiotics. Patients and operators will not be blinded. The primary endpoint will be hospitalization attributed to device or lead infection within 12 months of the procedure. Consent for de identified records will be obtained at the first postoperative visit. This is a simple study with a one-page baseline data form, and a single summary follow-up at 12 months entered in an iDatafax based data collection interface, with more detailed data collection in the 2% of patients expected to develop the primary endpoint.

Tissue Characterisitics of Peri-operative Myocardial Infarction as Measured by Cardiovascular MRI (CMR VISION) - Dr. Craig R. Butler (Mazankowski Alberta Heart Institute); $68,336; Cardiovascular Imaging Working Group

Each year millions of people suffer peri-operative myocardial infarction (MI) following non-cardiac surgery. There is a need to clarify the controversy surrounding the pathophysiology of peri-operative MI so that we may intervene safely and effectively with current and novel therapies. The VISION study is currently evaluating comprehensive risk predictive models for peri-operative MI, and its sub-study CTA VISION is investigating the ability of pre-operative Coronary CT angiogram to predict who will have a peri-operative MI. The CANNeCTIN Cardiovascular Imaging Working Group (CCIWG) is proposing a multicenter pilot project that leverages existing resources from CTA VISION and VISION to characterize the pathophysiology of peri-operative MI using cardiovascular magnetic resonance (CMR). CMR is a safe, non-radiating imaging modality with the unique ability to assess myocardial perfusion as well as accurately characterize tissue features of MI in vivo. CMR VISION will perform CMR scans on a total of 120 patients from CTA VISION and VISION who have had peri-operative MI. The objectives of CMR VISION are as follows: 1) To be the first research group to characterize the presence, size, location, perfusion, and biomolecular features of peri-operative MI following non-cardiac surgery, 2) To determine the mechanism of peri-operative MI by relating the vascular territory of MI to the preoperative coronary anatomy (i.e. from CTA VISION) and thereby determine the anatomy of the culprit coronary artery, and 3) To identify which CMR variables best predict thirty day mortality and major adverse cardiac events amongst patients who have experienced MI following non-cardiac surgery. The results of CMR VISION will not only help us improve our acute management of peri-operative MI, but will also provide a much needed tool with which to risk stratify patients who experience peri-operative MI.

Our congratulations to the many investigators, collaborators, and working groups involved in these projects!

Hamilton Health Sciences • Hamilton, Ontario • 905.521.2100