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Women With Chest Pain^_*

Expanding the Diagnostic Armamentarium

Department of Cardiovascular Medicine, Flinders University of South Australia, Adelaide, Australia.

Key Words: magnetic resonance imaging • coronary artery disease • myocardial ischemia • perfusion imaging

Currently well-established noninvasive tests for the diagnosis of coronary artery disease—exercise electrocardiography (ECG), stress echocardiography, and stress single-photon emission computed tomography (SPECT)—all have substantial limitations in women in predicting significant angiographic CAD. Exercise ECG, which is the most commonly performed noninvasive initial investigation for the diagnosis of stable angina, has a particular disadvantage of being poorly specific for obstructive CAD in women. Reported specificities (with regard to the presence of obstructive epicardial CAD) have ranged from 30% to 70%, which are much lower than the reported rates in men (4,5). SPECT imaging, with either exercise or pharmacological stress, is commonly used for the evaluation of women presenting with chest pain symptoms. Although experience with these techniques is extensive (6,7), diagnostic accuracy can be reduced in women by both breast tissue and obesity, causing false-positive results, especially in the anterior myocardial segments. In contrast, stress echocardiography has performed better, possibly as the result of selection bias. Three meta-analyses have reported specificities ranging from 76% to 79% and sensitivities ranging from 81% to 86% for stress echocardiography (6), although both exercise and pharmacological stress echocardiography remain principally limited by acoustic windows and the difficulty in detecting minor gradations of wall motion change, particularly in the setting of abnormal resting function.

During the last 15 years, cardiac magnetic resonance imaging (CMR) has emerged as an attractive noninvasive approach for the assessment of CAD/chest pain syndromes, offering spatial resolution superior to nuclear techniques without the use of ionizing radiation (8). Previous studies, mainly in men, evaluating the utility of perfusion CMR in assessing CAD have found moderate-to-high diagnostic accuracy (9,10). Diagnostic accuracy has been further augmented by the use of a higher field strength (increased signal to noise ratio, increased sensitivity) (11) and by the combination of perfusion with late gadolinium enhancement (reduced misreads due to artefact, increased specificity) (12). In this issue of iJACC (JACC: Cardiovascular Imaging), the article by Klem et al. (13) is the first to address the utility of CMR perfusion and late enhancement exclusively in women. In this prospective observational study, researchers enrolled 147 consecutive women with chest pain or other symptoms that were suggestive of CAD. The 1.5-T CMR assessment consisted both of adenosine-stress and rest perfusion, and delayed enhancement imaging. The CMR components were analyzed visually with a pre-specified algorithm that the authors had previously described (12).

So how did CMR perform in this difficult patient group? The authors' principle finding is that the combined CMR stress test had a sensitivity of 84%, specificity of 88%, with an overall diagnostic accuracy of 87% for the diagnosis of significant CAD, as defined by >70% stenosis on quantitative coronary angiography. Reflecting the nuclear cardiology literature, test sensitivity was reduced in women with single-vessel disease (71% vs. 100% compared with multivessel disease) and small left ventricular mass (69% vs. 95%). Although the specificity of the combined CMR stress test reported by Klem et al. (13) compares favorably with the specificities published in meta-analyses for exercise ECG, stress echocardiography, and stress SPECT; such comparisons are difficult to make because the inclusion criteria differ across studies, and all of them (including that of Klem et al.) suffer from significant selection bias. More direct-comparison studies of noninvasive modalities (in the same population) are needed.

A number of intriguing and unanswered questions have emerged from this study. Although commonly used as the standard of reference in such studies, quantitative coronary angiography is not the ideal gold standard because the functional significance of coronary obstruction and luminal stenosis are only moderately correlated. Hence, it would have been useful to know the relationship between the result of the initial noninvasive test (whether it be exercise ECG, stress echo, or stress SPECT) and the subsequent CMR perfusion finding.

Was there good concordance between the functional tests in these women? The authors do not provide complete information on the baseline and CMR characteristics of the patients with "false-positive" and "false-negative" findings. Clearly, coronary microvascular disease due to diabetes, hypertension, or cardiac syndrome X could account for some of the "false-positives" reported in this study. It would have been useful to know whether women with clinical features suggestive of cardiac syndrome X always had perfusion abnormalities evident visually or whether some of them had visually normal perfusion CMR. Although syndrome X has traditionally been viewed as giving rise to global subendocardial perfusion defect under stress (14), recent CMR literature on this has been contradictory (15,16).

Finally, what other imaging tools do we have to tease out the varied and disparate causes of chest pain in women? In some women without obstructive CAD, chest pain symptoms may be secondary to the coronary slow flow phenomenon (17) or related to metabolic abnormalities, resulting in a shift toward myocardial glucose metabolism. Cardiac magnetic resonance imaging spectroscopy has been used to identify alterations in high-energy phosphates, providing a direct assessment of metabolic myocardial ischemia. A recent prognostic report from the WISE (Women's Ischemia Syndrome Evaluation) study suggested that chest pain hospitalizations were greater in women with a reduced phosphocreatine/adenosine triphosphate ratio (<20%) and nonobstructive coronary arteries (18). Although offering interesting pathophysiological insights, CMR spectroscopy at 1.5-T remains limited by low spatial resolution, poor interstudy reproducibility, and limited availability. Both quantitative CMR perfusion imaging (19) and blood oxygen level-dependent magnetic resonance imaging (20) might offer diagnostic and mechanistic insights. Blood oxygen level-dependent magnetic resonance imaging is the only noninvasive imaging modality that currently has the potential to measure myocardial oxygenation directly in humans. It is more robust at a higher field strength (3-T) and, together with quantitative CMR perfusion, might allow the interrogation of subendocardial versus subepicardial ischemia, especially in the cohort of women with chest pain and normal coronary arteries. A number of catheterization laboratory-based assessment methods also are available, including techniques to assess coronary endothelial dysfunction and/or coronary microcirculation (intracoronary flow wire measurements, intracoronary acetylcholine), although their invasive nature precludes widespread applicability. Figure 1 outlines a proposed diagnostic algorithm for the evaluation of women symptomatic with chest pain.

View larger version (30K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Proposed Algorithm for the Evaluation of Women With Chest Pain BOLD = blood oxygenation level dependent magnetic resonance imaging; ECG = electrocardiography; MRI = magnetic resonance imaging; SPECT = single-photon emission computer tomography.

	Footnotes

 
^_* Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.

^_* Reprint requests and correspondence: Dr. Joseph Selvanayagam, Professor of Cardiovascular Medicine, Flinders University of South Australia, Director Cardiac MR & CT, Flinders Medical Centre, Adelaide 5042, Australia. (Email: joseph.selvanayagam{at}flinders.edu.au).

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