Cardiovascular Diseases, Cardiotoxicity, Fluorouracil Adverse Reaction, Malignancy, Colorectal Cancer, Oesophagus Cancer, Gastric Cancer, Pancreatic Cancer
Conditions
Keywords
Cardio-oncology, Cardiotoxicity, Fluoropyrimidine cardiotoxicity
Brief summary
Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.
Detailed description
Fluoropyrimidine (5-FU and Capecitabine) based chemotherapy regimens form the cornerstone of treatments for gastrointestinal (GI) cancers. Fluoropyrimidines however, are associated with the development of cardiovascular toxicity which can take on different forms including chest pain, myocardial infarction, arrhythmias, heart failure and sudden death. The underlying mechanisms of cardiovascular toxicity are not fully understood. The investigators will use quantitative cardiovascular magnetic resonance perfusion imaging, CT coronary angiography, extra-cardiac vascular assessments and serum cardiac biomarkers to improve insights into the pathophysiology of fluoropyrimidine cardiotoxicity. All enrolled participants in this two centre study will have GI cancers requiring treatment with fluoropyrimidine chemotherapy.
Interventions
DIAGNOSTIC_TESTCardiovascular magnetic resonance with stress perfusion
Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
DIAGNOSTIC_TESTCT coronary angiography
CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease
DIAGNOSTIC_TESTRetinal OCT angiography
Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
DIAGNOSTIC_TESTSublingual microscopy (GlycoCheck)
To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
DIAGNOSTIC_TESTSerum cardiac biomarkers (High sensitivity troponin, NT pro BNP)
Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Sponsors
University College, London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age \>18 years * Gastrointestinal malignancy * Receiving fluoropyrimidine chemotherapy
Exclusion criteria
* Participants unable or unwilling to provide consent * Participants that have a conventional contraindication for magnetic resonance imaging (MRI) including permanent implantable cardiac devices, ferromagnetic implants, pregnancy, large body size not fitting into the scanner bore and severe claustrophobia will be excluded * Participants that have a conventional contraindication for adenosine stress perfusion including a history of trifascicular block or of second-degree heart block or higher on ECG, or uncontrolled asthma. * Participants with significant renal impairment (eGFR\<30ml/min) * History of allergy to adenosine, gadolinium or iodinated contrast * Patients with terminal illness (life expectancy \<6 months) will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in left ventricular extracellular volume from baseline | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in left ventricular global longitudinal strain from baseline | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in left ventricular ejection fraction from baseline | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in sublingual perfused boundary region | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in sublingual capillary density | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in retinal vessel density | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
| Change in high sensitivity troponin T | 6 months | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment |
Countries
United Kingdom
Contacts
Primary ContactAderonke Abiodun, MBChB
Outcome results
None listed