Cardiac magnetic resonance myocardial perfusion imaging for detection of functionally significant obstructive coronary artery disease: A prospective study

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Abstract

Background

Cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI) is considered a state of the art non-invasive modality for the detection of reversible ischemia. Recent studies have shown its utility in the diagnosis of coronary artery disease (CAD) and superiority over other established techniques. However, only a few studies compared CMR-MPI against the invasive standard including fractional flow reserve (FFR) and clinical validation in non-specialized centers is scarce. The aim of this study was to validate CMR-MPI in a real-world clinical environment and to test its diagnostic accuracy in symptomatic patients with suspected CAD versus FFR as the reference standard of functionally significant disease.

Methods and results

103 symptomatic consecutive patients (62 ± 8.0 years, 66% males) with suspected CAD and intermediate or high probability of disease underwent sequential CMR and invasive coronary angiography (XA). The CMR protocol included stress-rest adenosine perfusion, SSFP cine imaging and late-enhancement imaging. Functionally significant CAD was defined as occlusive/sub-occlusive stenoses on XA or non-occlusive stenoses with a FFR measurement of < 0.80 in vessels > 2 mm. On a patient-based model, CMR-MPI had sensitivity, specificity, positive and negative predictive values of 89%, 88%, 85%, and 91%, respectively, with a global accuracy of 88%. On a vessel-based analysis, these values were 80%, 93%, 79% and 94%, respectively, with a global accuracy of 90%.

Conclusions

CMR-MPI had a very high accuracy for detection of functionally significant CAD as assessed by FFR in patients with intermediate to high pretest probability.

Introduction

Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in western countries [1]. Since CAD is treatable, efforts must focus on prevention and detection of the early stages of disease, avoiding progression to irreversible damage (myocardial infarction and heart failure) [2], [3]. Therefore, it is essential to develop reliable non-invasive methods, capable to correctly identify the presence of CAD and to guide management [4]. Nuclear Imaging and Stress Echocardiography are most established for the diagnosis of myocardial ischemia. However, these techniques are limited by low spatial resolution and/or exposure to ionizing radiation [5]. Single-photon emission computerized tomography (SPECT) is limited by attenuation artifacts contributing to false positive and balanced ischemia may lead to false negative results in the presence of multivessel disease. In recent years, cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI) has evolved into a robust technique and is starting to challenge previously established methods [6]. CMR-MPI integrates anatomic and functional information in a single exam, with high spatial and temporal resolution [7] without exposing the patient to harmful radiation [8], [9]. It compares favorably to SPECT, positron emission tomography, and invasive coronary angiography (XA) [10], [11], [12]. However, the majority of these studies have been conducted in highly specialized CMR centers and/or academic research facilities. Therefore, one may argue that diagnostic accuracy may not be the same in routine clinical practice of non-academic hospitals. In fact, the discrepant results between the single-center “CE-MARC” trial [13] – showing CMR-MPI superiority over SPECT – and the “MR-IMPACT II” multicenter clinical trial [14] – reporting non-inferiority – highlight the importance of this discussion.

Furthermore, most studies tested CMR-MPI against an anatomical standard as quantitative coronary angiography (QCA) as assessed by XA, which may underestimate the performance of this functional test. Only a few studies compared CMR-MPI against the functional reference-standard, fractional flow reserve (FFR), reporting excellent accuracy for the diagnosis of functionally significant CAD [15], [16].

We thought to evaluate the diagnostic performance of CMR-MPI for ischemia detection in the clinical setting of a tertiary non-academic cardiology center, using invasive FFR as the reference standard.

Section snippets

Population

During a 22-month period (February 2010 to November 2011) we prospectively screened 176 consecutive patients referred by general physicians to our hospital outpatient cardiology clinic due to clinical suspicion of CAD. Inclusion criteria of the study were: age > 40 years, symptoms compatible with CAD and ≥ 2 risk factors and/or a positive/inconclusive treadmill test. Exclusion criteria included unstable clinical status, previous myocardial infarction, previous coronary artery bypass grafting,

Results

All the 103 patients completed the study protocol without adverse effects. All CMR scans were performed within 9 ± 8 days before XA.

Discussion

The main finding of our study is that CMR-MPI has very good accuracy for the detection of functionally significant CAD in symptomatic patients with intermediate or high pre-test probability. Our results show the high sensitivity and specificity of CMR stress perfusion, both in patient- and in vessel-based analysis. These results were obtained in a real world clinical cardiology setting, using standard, widely available acquisition sequences and a common 1.5 Tesla clinical CMR scanner.

Funding sources

The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.

NB was funded by FCT (Fundação para a Ciência e Tecnologia, Portugal), under grant number SFRH/BD/45989/2008 and received grant support from the Portuguese Society of Cardiology and the

Acknowledgments

The authors would like to thank the radiographers David Monteiro, Nuno Almeida, Júlio Antunes and Pedro Rodrigues, as well as all the nurses involved in patient preparation, for their high-quality continuous support and hard work during the clinical CMR lists. Thanks are extended to the radiographers Mónica Carvalho, Daniel Leite and Wilson Ferreira for imaging management and data support. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing

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