Fibrosis in Chronic and Delayed Myocardial Infarction (FCDMI)

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.

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis; Carcinoid Syndrome; Chemotherapy Induced Systolic Dysfunction
• Intervention / Treatment: Diagnostic test: 68Ga-FAPI and 18F-AlF-FAPI PET-MR

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 180

Contacts and Locations

• Study Contact: Name: Krithika Loganath, MBBS; Phone Number: 07774365798; Email: kloganat@ed.ac.uk

Study Locations

• United Kingdom
  • Scotland
    • Edinburgh, Scotland, United Kingdom, NE7 7EY
      • Recruiting
      • University of Edinburgh
      • Contact: Krithika Loganath; Phone Number: 07774365798; Email: kloganat@ed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Diagnostic test: 68Ga-FAPI and 18F-AlF-FAPI PET-MR; Hybrid Cardiac PET-MR with 68Ga-FAPI and 18F-AlF-FAPI radiotracer
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.	Diagnostic test: 68Ga-FAPI and 18F-AlF-FAPI PET-MR; Hybrid Cardiac PET-MR with 68Ga-FAPI and 18F-AlF-FAPI radiotracer
Carcinoid syndrome; 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.	Diagnostic test: 68Ga-FAPI and 18F-AlF-FAPI PET-MR; Hybrid Cardiac PET-MR with 68Ga-FAPI and 18F-AlF-FAPI radiotracer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis activity: Standardised uptake values (SUV	SUV	1-2 years
Fibrosis activity:Tissue-to-Background Ratio	TBR	1-2 years

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Investigators: Study Chair: Marc Dweck, MBBS PhD, University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Anticipated): November 10, 2025
• Study Completion (Anticipated): November 10, 2025

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Neuroendocrine Tumors; Drug-Related Side Effects and Adverse Reactions; Carcinoid Tumor; Myocardial Infarction; Infarction; Aortic Valve Stenosis; Malignant Carcinoid Syndrome; Serotonin Syndrome
• Other Study ID Numbers: 300754

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No