Overview
This study evaluates the prognostic value of quantitative myocardial perfusion imaging using oxygen-15 water positron emission tomography in patients with clinically suspected or known coronary artery disease (main basket), and explores temporal changes in myocardial perfusion related to disease progression, underlying pathophysiological processes, or treatment-related effects (additional baskets).
Description
This open-label, national, multicentre phase III clinical trial employs a core basket-protocol design comprising one main basket cohort and ten additional basket cohorts. The main basket (up to 40 000 participants) evaluates the prognostic value of quantitative myocardial perfusion imaging using oxygen-15 water positron emission tomography (PET) in patients with clinically suspected or known coronary artery disease (one PET examination per participant). Prognostic performance will be assessed for both global and regional perfusion parameters, including rest and stress myocardial blood flow and myocardial flow reserve, in the overall study population and in pre-specified subgroups. The additional baskets aim to explore temporal changes in myocardial perfusion in coronary artery disease and related conditions (two PET examinations per participant), whether driven by disease progression, underlying pathophysiological processes, or treatment-related effects: A) Antianginal treatment basket cohort (n = 40 - 60, pre- vs. on-treatment, follow-up after 2 - 3 months); B) Heart failure treatment basket cohort (n = 40 - 60, pre- vs. on-treatment, follow-up after 2 - 3 months); C) Transcatheter aortic valve implantation basket cohort (n = 40 - 80, pre- vs. post-implantation, follow-up after 3 +/- 2 months); D) Chronic total occlusion basket cohort (n = 60 - 90, pre- vs. on-treatment/post-intervention, follow-up after 3 - 6 months); E) Anti-inflammatory treatment basket cohort (n = 40 - 60, pre- vs. on-treatment, follow-up after 6 +/- 2 months); F) Chronic kidney disease basket cohort (n = 40 - 60, baseline vs. follow-up after 12 +/- 2 months); G) Long-term dialysis basket cohort (n = 40 - 60, baseline vs. follow-up after 12 +/- 2 months); H) Kidney transplantation basket cohort (n = 40 - 60, pre- vs. post-transplantation, follow-up after 12 +/- 2 months); I) Takotsubo syndrome basket cohort (n = 15 - 20, acute phase vs. post-recovery, follow-up after full recovery); J) ST-elevation myocardial infarction basket cohort (n = 40 - 80, baseline (after recent revascularization) vs. follow-up after 6 +/- 2 months). In all baskets, blood samples will be collected when feasible and stored in a biobank for future research.
Eligibility
Inclusion Criteria: 1) Signed written consent (all baskets); 2) Female and male subjects ≥ 18 years (all baskets); 3) Clinically suspected or known coronary artery disease (all baskets); 4) Clinical indication for myocardial perfusion imaging in alignment with current evidence-based practice, clinical guidelines, and/or local routines (most baskets). In case of the additional basket cohorts, subjects must meet one of the following additional criteria: A) Antianginal treatment basket cohort: High pretest probability of coronary artery disease, angina pectoris as the primary symptom, no or recently initiated or inadequate antianginal treatment that can be withheld for a duration equivalent to 3 - 5 drug half-lives, and no prior history of coronary intervention; B) Heart failure treatment basket cohort: Newly diagnosed idiopathic dilated cardiomyopathy and no or recently initiated heart failure therapy; C) Transcatheter aortic valve implantation (TAVI) basket cohort: Severe aortic stenosis accepted for TAVI; D) Chronic total occlusion (CTO) basket cohort: Coronary CTO eligible for i) optimized medical treatment alone, ii) percutaneous coronary intervention, or iii) reducer stent implantation; E) Anti-inflammatory treatment basket cohort: Cardiac sarcoidosis with an indication for anti-inflammatory treatment; F) Chronic kidney disease (CKD) basket cohort: CKD of varying severity, defined as estimated glomerular filtration rate \< 60 ml/min/1.73 m2, not receiving maintenance dialysis at baseline; G) Long-term dialysis basket cohort: Maintenance dialysis in end-stage CKD; H) Kidney transplantation basket cohort: End-stage CKD under evaluation for kidney transplantation; I) Takotsubo syndrome basket cohort: Classic, hemodynamically stable acute Takotsubo syndrome; J) ST-elevation myocardial infarction (STEMI) basket cohort: Recently revascularized acute STEMI. Exclusion Criteria (All Baskets): 1) Contraindications for the used pharmacological stress agents; 2) Contraindications for PET/CT or PET/MR, such as severe claustrophobia or non-MR-conditional implants; 3) Inability to understand and adhere to all study-related procedures, including participant preparation; 4) Pregnancy or lactation.
