The Future Of Cardiac Magnetic Resonance Clinical Trials

July 18, 2022

The Future Of Cardiac Magnetic Resonance Clinical Trials

Cardiac magnetic resonance (CMR) has become an integral modality of cardiovascular clinical care over the past two decades, and its role in the imaging-guided diagnosis and management of heart disease, cardiomyopathy[1] , cardio-oncology, and vascular disease continues to evolve.

CMR’s advantages – including its availability, safety, and capability to provide corresponding anatomical, physiological, and functional data – mean that it can be ideal for clinical trials, and the further integration of CMR into clinical practice offers the potential for enhanced cost-effectiveness, efficacy, and safety.

What are the milestones of CMR in clinical trials to date? And how can CMR continue to be integrated into large-scale clinical trial design? These are two of the areas covered by an article on ‘The Future of Cardiac Magnetic Resonance Clinical Trials’, authored by researchers from the US, UK, Canada, Germany, Australia, and Spain. The document examined the attributes, limitations, and challenges of CMR’s integration into the future design and conduct of clinical trials.

CMR ‘the reference standard’

The article highlighted that CMR has become the reference standard for numerous cardiovascular measurements. Advancements in CMR image acquisition and postprocessing are described as providing a “virtual heart biopsy” to clinicians, supporting precision medicine with the provision of detailed myocardial structure, function, perfusion, and tissue characterization, and offering a safer alternative to tests that use ionizing radiation or iodinated contrast.

Because of these advantages, the article remarked that CMR imaging biomarkers are “particularly well suited as surrogate clinical trial endpoints for the evaluation of both novel pharmacological and invasive interventions”.

Various examples of CMR’s role in cardiovascular clinical trials were then summarized. We will cover these in the following section.

CMR’s role in clinical trials

The role of CMR in clinical trials in the following areas was summarized:

Stable coronary disease

The article pointed to “extensive clinical evidence” that shows the ability of CMR to accurately diagnose patients with hemodynamically significant coronary stenosis, and guide invasive coronary angiography and coronary revascularization in symptomatic patients. Studies highlighted included the MR-INFORM and CE-MARC 2 trials.

Acute myocardial infarction

Echocardiography was acknowledged as the first-line tool after an acute myocardial infarction (AMI) due to its ability to offer a rapid assessment, but CMR was singled out as “uniquely suited to address the spectrum of myocardial tissue characteristics as a result of the acute injury” and assessing the ischemic injury.

Two recent AMI clinical trials have demonstrated the high diagnostic and prognostic values of CMR. It has been found that delayed-enhancement CMR can lead to a new infarct-related artery (IRA diagnosis) or elucidate new nonischemic pathogenesis in a significant share of patients with non-ST-segment-elevation myocardial infarction. CMR has served as a surrogate endpoint of various novel therapeutic interventions in this area, and CMR parameters have the “capability to differentiate between reversible and irreversible myocardial damage”.

Valvular heart disease

Multicenter trials have evaluated the prognostic value of CMR-derived parameters in aortic regurgitation (AR), mitral regurgitation, and aortic stenosis (AS) with the aim to find thresholds to guide valve surgery. CMR is described as “especially useful” when the evaluation of valve lesion severity or ventricular volumes/function is compromised by conflicting information or poor-quality echocardiographic windows.

Chemotherapy toxicity

CMR offers important information in the early identification of structural and pathological changes in cancer patients. It provides higher precision and accuracy than echocardiography to detect small, early changes in chamber size, ventricular function, native T1 values, and global strain. CMR is praised for its versatility in allowing a comprehensive evaluation of a large spectrum of cardiovascular toxicities.


CMR tissue characterization techniques, such as late gadolinium enhancement (LGE), T1/T2 mapping, extracellular matrix volume fraction (ECV), and T2∗ assessment, were described as “established” in diagnosis, risk stratification, and guidance of management of nonischemic cardiomyopathies. ECV could be used as a surrogate endpoint in clinical trials of cardiac amyloidosis therapies, while T1  could be used in clinical trials of early treatment with enzyme replacement.

Arrhythmia risk stratification in heart failure

CMR can identify key structural findings in both ischemic cardiomyopathy and nonischemic cardiomyopathy to identify the best candidates for implantable cardioverter-defibrillators and is particularly well-suited to identifying the best pacing strategies in patients with heart failure undergoing cardiac resynchronization therapy.

Ablation of ventricular tachycardia

CMR can produce models of regional electrical conduction velocities to identify the critical isthmus for ventricular tachycardia ablations, while LGE can be used to create maps that simulate voltage maps generated with an invasive electroanatomic method.

Cardiac manifestations of coronavirus infections

A CMR study demonstrated cardiac involvement in 78% and ongoing inflammation in 60% of recovered COVID-19 patients. The article underlined the potentially “important role” of CMR in cardiac prognostication among patients with active and recovered COVID-19.

Infrastructure and Support for CMR Clinical Trials

The role of the Society for Cardiovascular Magnetic Resonance (SCMR) in providing resources and guidance to facilitate clinical trials in CMR was highlighted. The SCMR standardized imaging protocols 2020 update describes current recommendations for a range of general protocols, disease-specific protocols, post-processing and analysis. An SCMR Clinical Trials Taskforce is working to support collaborative clinical trial efforts.

The general role of CMR in clinical trials

The article identified four main ways that CMR can be used in clinical trials:

  • To identify appropriate patients for testing an intervention
  • To confirm similar distributions of key characteristics in treatment arms
  • To develop appropriate surrogate endpoints
  • To inform the development of very large studies with hard clinical endpoints based on surrogate endpoints evaluated in previous CMR studies

The authors went on to set out eight components of planning a clinical trial using CMR, which can be read in the full text of the article.

Role of AI and ML in CMR Clinical Trials

The ability of artificial intelligence (AI) to aid patient selection, acquisition of images, post-processing of data, and interpretation of sequences was highlighted, allowing physicians to quickly review a list of potential trials for patients. The article outlined the capability of AI and machine learning (ML) “to unravel the wealth of information contained in CMR images and potentially enhance patient diagnosis, prognosis, and outcome predictions”.

CMR can “play an integral part in clinical trials”

The document concluded that “CMR is well-suited to provide complementary information relative to other imaging modalities to help meet critical needs related to diagnosis and treatment of cardiovascular disease,”, and “is well-positioned to play an integral part in clinical trials with its ability to provide anatomical, physiological, and functional data in a single imaging session”.