Fibrosis in Chronic and Delayed Myocardial Infarction

Fibrosis in Chronic and Delayed Myocardial Infarction

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

1. In patients with aortic stenosis, myocardial fibrosis activity will correlate with markers of left ventricular decompensation and aortic valve fibrosis activity, will predict progression in fibrosis burden and will decline following aortic valve replacement.
2. Increased myocardial fibrosis activity will be observed in the early stages of anthracycline- induced cardiotoxicity and will predict later deterioration in cardiac function.
3. In patients with carcinoid syndrome, increased endocardial fibrosis activity will be observed in patients with subclinical and clinically significant valve involvement.

Inclusion Criteria:

Cohort 1(Aortic stenosis):

• Male or female above the age of 50 years old
• Provision of informed consent prior to any study specific procedures
• 25 patients with symptomatic severe aortic stenosis (peak velocity >4.0 m/s)
• 25 patients with moderate aortic stenosis (peak velocity 3.0-4.0 m/s)
• 10 patients with mild aortic stenosis (peak velocity 2.6-2.9 m/s)
• 10 patients with aortic sclerosis (tri-leaflet thickened aortic valve with no obstruction of ventricular outflow)
• 10 healthy volunteers (no other significant co-morbidities, as assessed by the study PI)

Cohort 2 (Chemotherapy-induced cardiotoxicity):

• Male or female over the age of 35 years with evidence of cardiotoxicity on cardiac MRI (performed as part of the Cardiac care study), at least 1 year after anthracycline treatment.
• 10 patients over the age of 35 years (male or females) without evidence of fibrosis on their 1-year scan after anthracycline treatment.
• 10 healthy volunteers (>35 years of age) with no significant co-morbidities, as assessed by the study PI.
• Provision of informed consent prior to any study specific procedures

Cohort 3 (Carcinoid syndrome):

• 30 patients with carcinoid syndrome (with or without cardiac involvement), over the age of 35 years, diagnosed as per consensus guidelines
• Provision of informed consent prior to any study specific procedures

Exclusion Criteria:

• Inability or unwilling to give informed consent.
• History of claustrophobia or feeling of inability to tolerate supine position for the MRI scans.
• Impaired renal function with eGFR of <30 mL/min/1.73m2.
• Women who are pregnant or breastfeeding.
• Contrast allergy
• Contraindication to cardiac MRI (e.g. metallic implant or severe claustrophobia)
• Recent myocardial infarction, other known causes of cardiomyopathy/cardiac fibrosis.