ACCELERATE-CMR for Coronary Artery Disease Detection

Background and clinical context Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide and is responsible for a substantial burden of healthcare utilisation. Appropriate management depends upon accurately identifying patients with clinically significant disease while avoiding unnecessary invasive investigation in those without functionally important coronary artery disease. Consequently, contemporary clinical guidelines recommend non-invasive imaging as the initial investigation for many patients with suspected chronic coronary syndromes before consideration of invasive coronary angiography (ICA).

Although ICA remains the reference standard for defining coronary anatomy, it is invasive, costly, exposes patients to ionising radiation and carries a small but important risk of complications. Furthermore, anatomical stenosis alone does not reliably indicate whether a lesion causes myocardial ischaemia, and a substantial proportion of patients undergoing ICA do not subsequently require coronary revascularisation. These limitations have driven a shift towards non-invasive imaging strategies that more appropriately select patients for invasive investigation.

Stress cardiovascular magnetic resonance (CMR) has become an established non-invasive imaging modality for the assessment of suspected CAD. It combines assessment of myocardial perfusion, ventricular function and myocardial scar within a single examination without exposure to ionising radiation, allowing comprehensive evaluation of both ischaemic heart disease and alternative cardiac pathology. Multiple prospective studies and randomised trials have demonstrated excellent diagnostic performance and have established stress CMR as an effective gatekeeper to ICA, reducing unnecessary invasive procedures while maintaining excellent clinical outcomes.

Despite these advantages, access to stress CMR remains limited by finite scanner capacity and prolonged examination times. Conventional stress CMR protocols typically require 45-60 minutes, limiting scanner throughput and contributing to prolonged waiting times in many healthcare systems. Expansion of CMR capacity through additional scanners and workforce growth is resource intensive, highlighting the need for more efficient use of existing imaging infrastructure.

Recent advances in pulse sequence design, accelerated image acquisition and streamlined workflow have created an opportunity to redesign stress CMR examinations while preserving the diagnostic information required for routine clinical decision making. Rather than simply accelerating individual imaging sequences, these developments allow optimisation of the entire imaging pathway using contemporary real-time cine imaging, streamlined late gadolinium enhancement imaging and stress perfusion imaging. The resulting accelerated protocol substantially reduces scan duration while maintaining the comprehensive nature of the CMR examination.

The accelerated protocol evaluated in ACCELERATE-CMR is the culmination of a structured programme of methodological and translational research undertaken by the study investigators. Early technical studies demonstrated the feasibility and reproducibility of accelerated image acquisition techniques and simplified imaging workflows. Subsequent prospective clinical evaluation demonstrated that an accelerated protocol reduced examination time from approximately 45-60 minutes to 15-20 minutes while maintaining excellent agreement with conventional stress CMR and substantially improving patient comfort and overall scan acceptability.

Although these findings provide strong support for accelerated stress CMR, demonstration of diagnostic agreement alone is insufficient to justify implementation within routine clinical practice. The value of a diagnostic investigation depends not only upon technical performance but also upon its influence on subsequent patient management. Even a technically accurate imaging test may lead to unnecessary downstream investigations if clinicians lack confidence in the findings, whereas an efficient imaging strategy that maintains diagnostic confidence has the potential to improve patient care, optimise healthcare resource utilisation and increase access to high-quality imaging.

ACCELERATE-CMR has therefore been designed as a pragmatic multicentre randomised controlled clinical effectiveness trial evaluating an imaging strategy rather than simply comparing imaging protocols. The study will recruit approximately 2,022 adults referred for routine clinical stress perfusion CMR across multiple NHS centres. Participants will be randomised to undergo either an accelerated or conventional stress CMR examination using standard clinical CMR systems, adenosine stress and gadolinium contrast administration. Subsequent investigations and treatment will remain entirely at the discretion of the treating clinical teams, allowing assessment of the imaging strategy under routine clinical conditions.

The principal objective is to determine whether accelerated stress CMR is non-inferior to conventional stress CMR with respect to downstream clinical effectiveness. In addition to evaluating patient outcomes, the trial incorporates assessment of patient experience, healthcare resource utilisation and cost-effectiveness, recognising that successful implementation of new diagnostic technologies requires evidence extending beyond diagnostic accuracy alone.

If accelerated stress CMR demonstrates equivalent clinical effectiveness while substantially reducing examination duration, implementation could increase scanner throughput, improve patient access to guideline-recommended cardiac imaging, reduce waiting times and enhance the efficiency of existing MRI services without requiring major additional infrastructure. The findings are therefore expected to provide evidence directly relevant to patients, clinicians, healthcare providers and policymakers considering wider implementation of accelerated stress CMR within routine clinical practice.

Study objectives The overall aim of the study is to assess the efficacy of an accelerated stress-CMR protocol with a view to increasing the utilisation of CMR in the diagnostic assessment of patients with suspected CAD. The primary hypothesis is that an accelerated stress CMR strategy is non-inferior to conventional stress CMR with respect to the primary composite endpoint of unnecessary ICA, unplanned revascularisation or additional noninvasive testing. In addition, it is hypothesised that patients undergoing the accelerated examination will report greater acceptability, reduced anxiety and an improved overall experience because of the substantially shorter examination. From a healthcare perspective, the investigators further hypothesise that reducing scan duration will increase scanner throughput, improve utilisation of existing infrastructure and improve cost-effectiveness without requiring additional capital investment or changes to routine clinical management.

Importance of study objectives The objectives have been selected to reflect outcomes that are important to patients, clinicians and healthcare systems. While maintaining diagnostic quality is essential, successful implementation also requires demonstration that a new imaging strategy maintains clinician confidence, avoids unnecessary downstream investigations, preserves patient outcomes and improves the efficiency of healthcare delivery. It is anticipated that ACCELERATE-CMR will generate evidence to inform future implementation of accelerated stress CMR within routine clinical practice and healthcare policy.

Study Design and Study Procedures ACCELERATE-CMR is a prospective, multicentre, pragmatic, open-label, parallel-group randomised controlled trial designed to evaluate the clinical effectiveness of an accelerated stress CMR strategy compared with a conventional stress CMR strategy. The study is conducted within routine NHS clinical practice and has been designed to reflect real-world delivery of cardiac imaging services.

Approximately 2,022 adults referred for routine clinical stress perfusion CMR will be recruited across multiple UK hospitals with established expertise in CMR. Participating centres use established clinical imaging pathways and experienced multidisciplinary teams, allowing evaluation of the imaging strategy under conditions representative of routine practice.

Randomisation Eligible participants who provide written informed consent will be randomised in a 1:1 ratio to undergo either accelerated or standard stress CMR. Randomisation will be undertaken using a secure, centralised web-based electronic system managed independently by the Robertson Centre for Biostatistics Clinical Trials Unit, ensuring allocation concealment until the point of randomisation.

Because the intervention involves two imaging protocols with substantially different examination times, blinding of participants and imaging staff is not feasible. However, downstream clinical management will follow routine practice, and predefined clinical outcomes will be adjudicated according to the trial protocol.

Baseline Assessment Following enrolment, baseline demographic characteristics, cardiovascular risk factors, relevant medical history, medication use and clinical status will be recorded. Standard clinical observations and routine investigations performed as part of usual care will be documented where available. Participants will complete validated patient-reported outcome measures evaluating health-related quality of life, angina symptoms and MRI-related anxiety and acceptability.

Intervention and Comparator Participants allocated to the control group will undergo a conventional stress CMR examination performed according to routine local clinical protocols. Participants allocated to the intervention group will undergo an accelerated stress CMR protocol.

Both groups will undergo clinically indicated pharmacological stress using adenosine together with gadolinium-based contrast administration. Images will be interpreted by appropriately trained clinicians according to routine clinical practice. The study does not prescribe subsequent investigations or treatment decisions, allowing clinicians to manage participants according to current standards of care.

Clinical Management A fundamental principle of ACCELERATE-CMR is preservation of routine clinical pathways following imaging. The trial evaluates an imaging strategy rather than a treatment intervention. Consequently, reports generated from the CMR examination will be returned to the referring clinical teams in the normal manner, and decisions regarding further investigation, invasive coronary angiography, coronary revascularisation or medical therapy will remain entirely at the discretion of the treating clinicians.

Follow-up Participants will undergo protocol-defined follow-up to capture downstream diagnostic investigations, coronary angiography, coronary revascularisation procedures, major adverse cardiovascular events, healthcare utilisation and patient-reported outcomes. Follow-up information will be obtained using participant questionnaires, review of medical records and routine healthcare data sources where appropriate. Collection of resource utilisation data will support the planned health economic evaluation.

Trial Governance The study is sponsored by the University of Leicester and managed in collaboration with the Robertson Centre for Biostatistics Clinical Trials Unit. Independent oversight is provided through Trial Steering Committee governance and independent clinical endpoint adjudication in accordance with the study protocol. Data are collected using a secure electronic data capture system with predefined validation procedures to promote data quality and consistency across participating centres.

Inclusion criteria

• patients >18 years of age referred for routine clinical stress CMR:
• A) with chest pain or angina equivalent OR

o B) with heart failure/suspected heart failure and referred for diagnosis of suspected CAD or evaluation of heart failure aetiology

• Willing and able to consent to participate in the trial

Exclusion criteria

• standard exclusion criteria for clinical stress CMR i.e.:

• absolute contraindications to CMR (non-conditional cardiac implantable electronic devices, metallic implants/foreign bodies),
• contraindications to adenosine (severe pulmonary disease, sinus-node/high-grade atrioventricular disease)
• severe kidney dysfunction (estimated glomerular filtration rate [eGFR] <30ml/min/1.73m2)
• uncontrolled arrhythmia or unstable chest pain
• severe claustrophobia
• previous invasive coronary angiography (within 12 months) with normal angiographic assessment and referred for CMR diagnosis of CMD