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In this study the investigators aim to examine the role that fibrosis plays in heart conditions such as aortic stenosis , chemotherapy-induced cardiotoxicity and carcinoid syndrome . Fibrosis is a common final result following any injury to the heart muscle and the investigators aim to identify this process early and in its active state. This will be examined by using a radiotracer 68Ga-FAPI or 18F-AlF-FAPI and PET-MRI or PET-CT.
The investigators aim to investigate the role of fibrosis activity using 68Ga-FAPI and 18F-AlF-FAPI PET in chronic and delayed valvular, myocardial and endocardial injury states, in particular aortic stenosis, chemotherapy induced cardiotoxicity and carcinoid heart disease. The investigators also aim to analyse serum markers of myocardial injury and fibrosis at different time-points in these patient cohorts.
Research Hypothesis
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aortic stenosis | The investigators will recruit 70 patients with aortic stenosis (25 patients with asymptomatic moderate aortic stenosis and 25 patients with symptomatic severe aortic stenosis, 10 patients with mild aortic stenosis and 10 patients with aortic sclerosis) and 10 healthy volunteers, who will undergo baseline 68Ga-FAPI or 18F-AlF-FAPI PET/MR imaging to establish fibrosis activity in healthy myocardium and in context of chronic myocardial injury. All patients will have a follow up FAPI PET/ MR scan 1 year after their baseline scan to assess whether myocardial fibrosis activity reverses following aortic valve replacement and restoration of normal afterload in patients with severe aortic stenosis and if baseline myocardial fibrosis activity can predict progression in the fibrosis burden and clinical progression in patients with mild or moderate aortic stenosis or aortic sclerosis. Healthy volunteers will not undergo any repeat imaging. |
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| Chemotherapy-induced cardiotoxicity | The investigators will recruit 60 patients who have undergone anthracycline treatment >1 year from enrollment and 10 healthy volunteers as part of this cohort. This will include 50 patients who have either clear evidence of cardiotoxicity (Ejection fraction <50% and a 10%point fall in ejection fraction) or a subclinical cardiac injury (elevated troponin, elevated T2, impaired global longitudinal strain) and 10 patients with no evidence of cardiotoxicity on their cardiac MRI scan (performed as part of the ongoing Cardiac CARE study). These patients will undergo baseline FAPI PET/MR imaging to establish the extent and pattern of myocardial fibrosis activity in context of delayed myocardial injury (chemotherapy-induced cardiotoxicity). All patients will have a follow up cardiac MRI scan 1-2 years after their baseline scan to assess whether baseline fibrosis activity is associated with a deterioration in cardiac function. Healthy volunteers will not undergo any repeat imaging. |
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| Carcinoid syndrome |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 68Ga-FAPI and 18F-AlF-FAPI PET-MR | Diagnostic Test | Hybrid Cardiac PET-MR with 68Ga-FAPI and 18F-AlF-FAPI radiotracer |
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| Measure | Description | Time Frame |
|---|---|---|
| Fibrosis activity: Standardised uptake values (SUV | SUV | 1-2 years |
| Fibrosis activity:Tissue-to-Background Ratio | TBR | 1-2 years |
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Inclusion Criteria:
Cohort 1(Aortic stenosis):
Cohort 2 (Chemotherapy-induced cardiotoxicity):
Cohort 3 (Carcinoid syndrome):
Exclusion Criteria:
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Cohort 1: 70 patients with aortic stenosis with 10 matched healthy volunteers Cohort 2: 60 patients with Chemotherapy-induced cardiotoxicity and 10 healthy volunteers Cohort 3: 30 patients with carcinoid syndrome
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Krithika Loganath, MBBS | Contact | 07774365798 | kloganat@ed.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Marc Dweck, MBBS PhD | University of Edinburgh | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Edinburgh | Recruiting | Edinburgh | Scotland | NE7 7EY | United Kingdom |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| D020230 | Serotonin Syndrome |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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In collaboration with the South East Scotland NET Service, the investigators will recruit 30 patients with carcinoid syndrome for this cohort. These patients will undergo a baseline echocardiogram and a FAPI PET/MR scan to investigate fibrosis activity within the cardiac chambers and valves. The investigators will recruit patients with established cardiac involvement as well as carcinoid syndrome patients with high circulating 5-HT concentrations who have no evidence of valve disease on echocardiography. All patients will have a follow up cardiac MRI scan and an echocardiogram, 6 months - 1 year after their baseline scan to assess whether baseline fibrosis activity is associated with subsequent deterioration in cardiac and valvular function. |
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| D014694 |
| Ventricular Outflow Obstruction |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |