Hypertrophic Obstructive Cardiomyopathy
Conditions
Keywords
endothelial progenitor cells, aspirin, acetylsalicylic acid, alcohol septal ablation
Brief summary
Aspirin at doses used during acute myocardial infarction may inhibit the mobilization of endothelial progenitor cells (EPCs).
Detailed description
Aspirin has been shown to lower the number of EPCs in a time- and concentration-dependent manner. In vitro studies also show that aspirin may reduce the migratory and adhesive capacity of isolated EPCs, inhibit iNOS and tubule formation, which are pre-requisites for angiogenesis. This is relevant when patients are given a loading dose of 325mg at the time of diagnosis of acute myocardial infarction where higher numbers of EPCs have been associated with better outcomes. Furthermore, in the PLATO (Platelet Inhibition and Patient Outcomes) trial, high dose aspirin appeared to counteract the beneficial effect seen when ticagrelor or clopidogrel was used with low doses of aspirin in acute coronary syndromes (ACS). As aspirin is currently standard of care in the management of ACS, it is difficult to conduct a study of the effect of aspirin versus placebo in that scenario. However, during alcohol septal ablation for hypertrophic obstructive cardiomyopathy, the indication for an antiplatelet agent is not well defined and varies between operators. When a small amount of myocardium is deliberately destroyed in this process, it serves as an ideal model to study the effect of aspirin on the biology of EPCs in vivo. This could provide an explanation to the different effects of high versus low dose aspirin when combined with a second antiplatelet agent in the management of ACS.
Interventions
DRUGAspirin
Aspirin 325mg bolus followed by 162mg daily until day 7 post alcohol septal ablation
Sponsors
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who have been selected to undergo alcohol septal ablation for hypertrophic obstructive cardiomyopathy based on clinical need 2. Age \>18 years, \<80 years
Exclusion criteria
1. Patients with known allergy to aspirin 2. Inability or refusal to consent to participate in the study 3. Patients who are on non-steroidal anti-inflammatory drugs and cannot be stopped for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint | 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days | Change in number of EPCs measured at 0 (baseline), 1, 6, 24, 72 hours and on day 7 post procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial cell migration in vitro compared to baseline at any timepoint | 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days | Change in endothelial migration measured at 0,1, 6, 24, 72 hours and on day 7 post procedure |
Other
| Measure | Time frame | Description |
|---|---|---|
| Peak angiopoietin-2 level | 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days | Change in level of angiopoietin-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure |
| Peak SDF-1 level | 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days | Change in level of SDF-1 at 0, 1, 6, 24, 72 hours and on day 7 post procedure |
| Peak vascular endothelial growth factor (VEGF) level | 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days | Change in level of VEGF at 0, 1, 6, 24, 72 hours and on day 7 post procedure |
| Peak tie-2 level | 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days | Change in level of tie-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure |
| Peak angiopoietin-1 level | 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days | Change in level of angiopoietin-1 at 0, 1, 6, 24, 72 hours and day 7 post procedure |
Countries
Canada
Outcome results
None listed