Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints

Pitcher, Alex; Ashby, Deborah; Elliott, Paul; Petersen, Steffen E.

doi:10.1136/hrt.2011.225904

Cited by 24 publications

(17 citation statements)

References 72 publications

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“…In the context of clinical trials, this may lead to potentially important reductions in sample size (and hence cost) for a given power, statistical significance threshold and predicted treatment effect size ( Figure 18.1). 5,6 CMR is extremely versatile, and this versatility arises from the very wide range of pulse sequences available. 7,8 A limited number of sequences are typically required to answer specific questions and these can often be completed in a single study lasting B30-45 minutes.…”

Section: Overview Of the Current Status Of Cmr (Imaging And Spectroscmentioning

confidence: 99%

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Chapter 18. Cardiovascular Magnetic Resonance

Pitcher¹,

Karamitsos²,

Schneider³

et al. 2013

New Applications of NMR in Drug Discovery and Development

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Section: Overview Of the Current Status Of Cmr (Imaging And Spectroscmentioning

confidence: 99%

“…In the clinical phase, it can be used to identify suitable participants, to ensure baseline comparability of treatment arms and to generate markers of disease presence, severity or activity for use as outcome measures in clinical trials. 5 …”

mentioning

confidence: 97%

Chapter 18. Cardiovascular Magnetic Resonance

Pitcher¹,

Karamitsos²,

Schneider³

et al. 2013

New Applications of NMR in Drug Discovery and Development

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“…Given these limitations with the application of clinical end points in myocardial infarction trials, there has been significant interest in the use of surrogate imaging end points. One of the most important surrogate end points used in myocardial infarction trials has been the measurement of infarct size, initially using radionuclide techniques 118 and, more recently, contrast-enhanced CMR 119 ( Figure 12). Although the principal role of image-based infarct size measurements in myocardial infarction trials has been to assess the efficacy of novel therapies, the use of imaging has also provided unique mechanistic insights.…”

Section: Myocardial Infarct Imagingmentioning

confidence: 99%

The Future of Cardiovascular Imaging

2016

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O ver the past 2 decades, we have witnessed an explosive expansion in the armamentarium of noninvasive and invasive imaging technologies capable of providing detailed information about the structure and function of the heart and vasculature. Many of these technologies are integrative (eg, positron emission tomography and computed tomography, positron emission tomography and MRI), thereby compounding the unique strengths of the component technologies to achieve unprecedented improvements to our ability to diagnose disease, improve patient care, and advance biomedical research. In addition, the miniaturization of imaging devices with dramatic increases in sensitivity and spatial resolution, coupled with the development of quantitative molecular imaging approaches for evaluating physiology and pathobiology at the cellular and molecular levels, provides a unique platform for a new era in diagnostic imaging. The crucial role of imaging in early phenotyping of disease, risk assessment, and management guidance is expanding rapidly in ways previously thought unrealistic.Along with clinical, molecular, and genomewide association studies, structural and functional quantitative imaging already plays a critical role in phenotyping cardiovascular disease. Unique strengths of imaging phenotyping include its ability to provide precise, organ-specific anatomic localization and quantification of disease traits, to demonstrate and quantify involvement of other organs in cardiac disease, to provide an opportunity to investigate the time course of disease-specific molecular events in vivo, and to track their response to therapy. In so doing, quantitative structural and functional imaging can provide a nuanced description of disease burden (eg, atherosclerosis, myocarditis), disease subtypes (eg, amyloidosis), and, importantly, the relationship between the specific phenotype and outcomes, thereby informing treatment strategies and allowing more personalized approaches to patient management.Our objectives for this article are to (1) provide a viewpoint regarding the evolving role of cardiovascular imaging in biomedical research and clinical practice, (2) discuss the challenges associated with clinical translation of imaging innovations and the opportunities for multimodality imaging in the changing paradigm of value-based medicine, and (3) briefly outline future challenges and opportunities including the requirements for training future generations of imaging scientists and clinical specialists. Unlike traditional reviews that provide a detailed discussion of the role of 1 or more imaging modalities in cardiovascular (CV) disease, our discussion will focus on the potential role of imaging in what we believe are key areas of the translational highway with specific examples on how structural and functional imaging may contribute to scientific discovery, diagnosis, risk stratification, and patient management in each of those areas. Redefining the Role of Imaging Across the Continuum of Biomedical Research and Clinical Practice Translati...

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“…To the Editor We read with great interest the recent review article by Alex Pitcher and coworkers highlighting the role of cardiac MRI as a surrogate end point in clinical trials 1. The authors focus on vascular imaging, measurement of infarct size by late gadolinium enhancement (LGE) and measurement of ventricular volumes, mass and function.…”

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Cardiac MRI as end point in clinical trials

Eitel

Desch

Thiele

2011

Heart

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To the Editor We read with great interest the recent review article by Alex Pitcher and coworkers highlighting the role of cardiac MRI as a surrogate end point in clinical trials. 1 The authors focus on vascular imaging, measurement of infarct size by late gadolinium enhancement (LGE) and measurement of ventricular volumes, mass and function. However, several promising surrogate end points especially in the setting of acute myocardial infarction are missing and should be also brought to the reader's attention.Recently, T2-weighted MRI of myocardial oedema has been established as a robust measure of myocardium at risk. Therefore, the salvaged myocardium at risk can be measured as the difference between the area at risk and final infarct size (LGE). 2 Myocardial salvage assessed by MRI is independently associated with hard clinical end points, and there are advantages of measuring the salvaged area at risk over infarct size. 2 Infarct size depends on multiple factors such as extent of area at risk, collateral blood flow, duration of myocardial ischaemia and metabolic demand. Thus, myocardial salvage with an adjustment for the area at risk may be a better surrogate end point in clinical trials investigating the efficacy of novel reperfusion strategies.Another important surrogate end point not mentioned in the paper is microvascular obstruction (MO) as a marker of microvascular damage/no-reflow. Areas of impaired microcirculatory flow can be directly visualised and quantified by LGE MRI appearing as central dark zones within the infarcted area. The presence and extent of such MO have shown incremental prognostic value above traditional prognostic markers and may be another promising marker to evaluate new strategies to reduce reperfusion injury. 3 Finally, recent studies have demonstrated the potential of MRI to detect intramyocardial haemorrhage (IMH) as a marker of severe reperfusion injury. IMH has been shown to be an independent predictor of adverse left ventricular remodelling irrespective of the initial infarct size and MO and has additional prognostic value after infarction. 4 Therefore, the ability to visualise IMH adds another reason for the application of MRI as an end point in clinical infarction trials, which can obtain a variety of strong prognostic markers (left ventricular function/volumes, infarct size, myocardial salvage, MO and IMH) in a single scan.

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Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints

Cited by 24 publications

References 72 publications

Chapter 18. Cardiovascular Magnetic Resonance

Chapter 18. Cardiovascular Magnetic Resonance

The Future of Cardiovascular Imaging

Cardiac MRI as end point in clinical trials

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