Coronary artery disease: Clinical presentation, diagnosis and prognosis in women

Nutrition, Metabolism & Cardiovascular Diseases (2010) 20, 426e435 available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/nmcd

REVIEW

Coronary artery disease: Clinical presentation, diagnosis and prognosis in women C. Leuzzi*, M.G. Modena Department of Cardiology, University Hospital of Modena, Modena, Italy Received 10 July 2009; received in revised form 1 February 2010; accepted 18 February 2010

KEYWORDS Women; Coronary heart disease; Clinical characteristics; Diagnostic tests; Prognosis

Abstract Recent advances in the field of cardiovascular medicine have not led to significant declines in case-fatality rates for women as in men. There are gender-specific differences in symptoms profile, diagnosis and treatment of coronary disease in women. For women presenting for coronary heart disease (CHD) evaluation, traditional disease management approaches that focus on detection of a ‘critical stenosis’ often fail to identify those women critically at-risk. Symptoms do not help physicians in differential diagnosis of chest pain in women; indeed the most common presentation of obstructive CHD in women is atypical symptoms. In 50% of the cases, non-obstructive CHD at coronary angiography, due to ‘noncardiac chest pain’ or coronary microvascular dysfunction is frequently reported. For these reasons, the evidence reviewed suggests that prognostic risk assessment may work relatively better than diagnostic obstructive coronary disease assessment for women. ª 2010 Elsevier B.V. All rights reserved.

Coronary heart disease (CHD) is the most common cause of death amongst women, who experience more complications after acute myocardial infarction (AMI) than men [1]. By contrast, breast cancer accounts for just 3% of all deaths in the female adult population [2]. Recent advances in the field of cardiovascular medicine have not led to significant drops in case-fatality rates for women, compared to the dramatic reductions achieved for men [3]. The gender-specific difference in cardiovascular disease mortality provides additional support for a lack of comparable progress in population-based risk reduction efforts for women [4]. * Corresponding author.

Supplementary evidence has observed significant delays in health-care-seeking behaviour, less intensive resource use patterns and longer diagnosis times for women than men. Available data indicate that women are less likely to be referred for coronary angiography and revascularisation procedures than men, and referral tends to occur at a later stage in the disease process [5,6]. Pharmacological therapy is hampered by defective evidence, as women are frequently underrepresented in clinical trials and there may be gender differences in therapeutic response [2]. For example, women experience more bleeding than men regardless of whether they are treated with glycoprotein (GP) IIb/IIIa inhibitors, most likely due to frequent excess dosing in women [7].

0939-4753/$ - see front matter ª 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2010.02.013

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Although a lower intensity of care may be, in part, related to a differential clinical history, symptom profile and acuity of presentation, under-recognition of this condition in women may also be contributory to worsening outcome, especially in women with an established diagnosis of ischaemic heart disease or AMI [8]. Over the past 2 decades, many important studies have helped develop accurate clinical tests, risk factors, preventive interventions and effective therapies for CHD. Unfortunately, many of these studies have either excluded women entirely or included only limited numbers of women and minorities. Thus, much of the evidence supporting contemporary recommendations for testing, prevention and treatment of coronary disease in women is extrapolated from studies conducted predominantly on middle-aged men [9]. Applying the findings of studies on male cohorts for the management of CHD in women may be in appropriate, since the symptoms of CHD, natural history and response to therapy are different in men and women [10]. The fact that CHD is often fatal, and that nearly two-thirds of women who die suddenly have no previously recognised symptoms, make preventing CHD all the more important [11]. This review will briefly outline the major cardiovascular risk factors and common clinical presentation of coronary artery disease in women, with particular focus on the screening value of different non invasive testing for a better clinical stratification and improvement of cardiovascular events prediction between gender.

Risk factors For the sizeable proportion of women presenting for CHD evaluation, traditional disease management approaches that focus on detecting ‘critical stenosis’ often fail to identify those women who are critically at-risk [4]. Guidelines emphasise the importance of recognising the full spectrum of cardiovascular disease and thus classify women as being at high risk, intermediate risk, lower risk and optimal risk (Table 1) [11]. Table 1

Classification is based on clinical criteria and/or the Framingham global risk score. The role that novel cardiovascular disease risk factors (e.g., high-sensitivity C-reactive protein) and recently developed screening technologies (e.g., coronary calcium scoring) should play in guiding preventive interventions is as yet unclear. New findings support the concept of a multifactorial model, in which sex hormones interact with traditional and conditional risk markers, leading to an increase in the functional expression of atherosclerotic plaque deposition or vascular or metabolic alterations resulting in worsening outcomes for women [8]. Whereas the risk factors are the same in both sexes, gender-specific differences are noted (Table 2) [12]. Evidence is fair to good for the roles of hyperlipidaemia, diabetes and hyperhomocysteinaemia as risk factors, but weak for other risk factors. Age, diabetes, and levels of certain lipoproteins were stronger risk factors for women than for men [13]. Diabetes mellitus is the most important risk factor and CHD mortality is 3e5 times higher in diabetic compared to non-diabetic women, whereas the risk is 2e3 times higher in diabetic men [14]. It would also seem that pre-menopausal diabetes eliminates the ‘female advantage’ of a predominately lower CHD prevalence and outcome risk that exists for the female population in general [15]. The relatively higher risk for ischaemic heart disease associated with diabetes in women is still to a great extent unexplained [16]. At the onset of diabetes-related cardiovascular complications, women have higher out-of-hospital mortality than men, and those who reach hospital are more likely to die from an initial cardiac event and are also at high risk of post-event complications [17]. Population studies have noted that total cholesterol measurements are higher in men up to the fifth decade of life however, beyond this age, women have higher values [18]. Hypertriglyceridaemia is also a more potent independent risk factor for CHD in women than in men [19]. Other factors are unique to the female, such as menopause, whose effect is all the more important when it

Spectrum of CVD Risk in Women [11].

Risk group

Framingham global risk (10-y absolute CHD risk)

Clinical examples

High risk

>20%

Intermediate risk

10e20%

Lower risk

<10%

Optimal risk

<10%

Established CHD Cerebrovascular disease Peripheral arterial disease Abdominal aortic aneurysm Diabetes mellitus Chronic kidney disease Subclinical CVD (e.g., coronary calcification) Metabolic syndrome Multiple risk factors Markedly elevated levels of a single risk factor First-degree relative(s) with early-onset (age: <55 y in men and <65 y in women) atherosclerotic CVD May include women with multiple risk factors, metabolic syndrome, or 1 or no risk factors Optimal levels of risk factors and heart-healthy lifestyle

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Table 2 Comparison of gender differences in conventional risk factors [12]. Men Risk factor threshold values Age threshold for [ disease risk Family history of premature CHD HDL cholesterol Population average values Lipids Total cholesterol HDL cholesterol Prevalence, rates Hypertension Smoking Coronary disease or outcome, risk Triglycerides Diabetes mellitus Obesity (e.g., BMI 30 kg/m2) Central obesity (>35 kg/m2)

dysfunction at baseline was associated with development of diabetes, again over a 4-year period [23].

Women

Clinical presentation 45 yrs

55 yrs

<55 yrs

<65 yrs

<50 mg/dl

[

[ For women after age w50 yrs [

[ [

[

[ [ [ [

occurs early, and hypothalamic hypoestrogenism in fertile women. Gender-specific opportunities for identifying women’s risk (e.g., during pregnancy) also deserve further exploration. For example, pre-eclampsia may be an early indicator of cardiovascular risk. Furthermore, maternal placental syndromes associated with conventional cardiovascular risk factors may be additive in defining cardiovascular risk in women [4]. Besides the conventional risk factors, new-advent risk indicators such as inflammatory markers (for instance highsensitivity C-reactive protein, interleukin (IL)-6, fibrinogen and acute phase protein), retinal artery narrowing, coronary artery calcification, endothelial dysfunction and anaemia are therefore now being studied in women [20]. Women are also at a higher risk of inflammatory and auto-immune disease [21]. It is postulated that decades of relatively higher levels of inflammation, coupled with the clustering of risk factors that occurs with the loss of oestrogen during menopause, may be associated with more frequent endothelial dysfunction, a loss of arterial compliance, and dysfunction in the microvasculature, resulting in more frequent myocardial flow heterogeneity in women [4]. Endothelial dysfunction is common after the menopause and its detection may precede overt disease such as hypertension and diabetes. For example, in a cohort of normotensive healthy women, development of endothelial dysfunction, as evaluated as flow-mediated dilation with brachial ultrasound, was associated with hypertension over a 4-year follow-up period [22]. Similarly, in another cohort of euglycaemic non-obese women, marked endothelial

In approximately 60% of cases, the initial presentation of CHD in women is acute myocardial infarction (AMI) or sudden cardiac death and up to half of all women presenting with an AMI report no prior chest pain symptoms [8,24]. After sudden cardiac death, the most common presentation of obstructive coronary heart disease for women is atypical symptoms, such as back pain, dyspnoea, indigestion, nausea/vomiting and weakness [12,25]. Furthermore, women reported more pain in the jaw and neck than men and they were more likely to describe their chest pain as a feeling of fullness than men [25]. Males were more likely to have chest pain. The ‘typical’ female presentation of signs and symptoms of CHD is more complex and multifactorial than that of men [12]. Not surprisingly, patients with myocardial infarction with ST-segment elevation in the Global Registry of Acute Coronary Events (GRACE) study were less likely to receive percutaneous coronary intervention or fibrinolysis if their symptoms were atypical (no chest pain) [26]. Despite the reported gender differences, typical symptoms are significantly associated with acute coronary sindrome (ACS) in women [27]. Women often appear to have a greater number of associated symptoms as part of their ACS presentation than men [28]. There are multidimensional factors that contribute to different symptoms being observed in men and women. For this reason, some authors constructed an organising framework representing the multidimensional factors to explain differences between women and men in their perception of symptoms of ACS. Type, severity, location and quality of symptoms may vary because of the psychosocial, physiological, anatomical and biological differences between women and men (Fig. 1) [25]. Women suffer more acute than prodromal symptoms. The most frequent prodromal symptoms experienced more than 1 month before AMI were unusual fatigue (70.7%), sleep disturbance (47.8%) and shortness of breath (42.1%) [29]. A small proportion of patients (about 16%) with ACS seeks medical assistance for prodromal symptoms in the 90 days before the event. Seeking treatment for these symptoms is associated with improved survival in women but not in men, since prodromes were associated with improved 1-year survival for women but not for men [30]. There would appear to be an interaction effect of symptom presentation with age, in that older women often present in a similar way to men. This would include the fact that older women more frequently experience typical angina. However, women <65 years are also 50% more likely than younger men to be discharged with a diagnosis of unstable angina [4]. For patients with stable, intermittent chest pain, their description of pain is the most important predictor of CHD and may be a factor that contributes to less intensive management for female patients [31]. Particularly for diabetic patients, symptoms are generally not as effective guides to CHD risk as objective evidence of ischaemia. Diabetes is an independent

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Figure 1 Framework to explain differences between women and men in their perception of symptoms of acute coronary syndromes.

predictor of ‘atypical’ presentation of AMI in women, and research to date suggests that shortness of breath may be an important ACS symptom in women with diabetes [17,32]. Chest pain typical of angina pectoris is less likely to be associated with obstructive epicardial CHD in women than in men [4]. For example, in one study, 41% of women referred with chest pain, who subsequently underwent coronary angiography, were found to have normal coronary arteries, compared with only 8% of men referred under similar circumstances [33]. Coronary angiography is one of the procedures most frequently performed in women; however, non-obstructive (i.e., <50% stenosis) CHD is frequently reported [34]. Most women with non-obstructive CHD at coronary angiography continue to experience symptoms that contribute to a poor quality of life and high health-care resources use due to repeated examinations and hospitalisations [35,36]. Pain is a more prominent factor affecting health-care costs and disability for women than men. In fact, women with nonobstructive CHD used a greater proportion of their total costs for anti-ischaemic therapies compared with women with 1-vessel to 3-vessel CHD [34]. Although many of these women are diagnosed with ‘noncardiac’ chest pain, an alternative mechanism for their symptoms is coronary microvascular dysfunction. Differentiation between these mechanisms of chest pain is important, because ‘noncardiac’ chest pain is not associated with cardiovascular sequelae and may require further medical evaluation and treatment. By contrast, syndrome X, which is thought to be caused by microvascular dysfunction, is associated with inducible metabolic ischaemia and can be treated by improving microvascular vasomotor tone with oral L-arginine, a precursor to vascular nitric oxide, and oestrogen [36]. However, the prevalence of coronary microvascular dysfunction in women with chest pain in the absence of obstructive CHD is uncertain. Furthermore, most of these patients have an ‘abnormal’ exercise stress test, myocardial perfusion defects on gated Single-photon emission computed tomography (SPECT) or stress-induced wall motion abnormalities on echocardiography. One study

demonstrated that coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of angiographically documented obstructive CHD [36]. Current limitations on health-care resources emphasise the need for better identification of those women most likely to have coronary artery disease before referral for invasive assessment [33].

Role of several non-invasive diagnostic tests in the diagnosis and prognosis in women with suspected CAD Lower use of non-invasive diagnostic testing at this initial point of care may translate into delayed diagnosis, delayed initiation of therapeutic interventions, and ultimately, worse outcomes [37]. Conventional diagnostic tests that focus on identifying obstructive disease do not work as well for women as for men. The indirect evidence reviewed here suggests that prognostic risk assessment (e.g., detection of the culprit patient) may work relatively better for women than diagnostic obstructive coronary disease assessment (e.g., detection of the culprit stenosis). Evaluation of the prevalence and mechanism of microvascular dysfunction in women with chest pain may provide the basis for early diagnosis. There are many diagnostic tests that indirectly describe coronary microvascular function using non-invasive imaging techniques in women with angina and normal coronary artery on angiogram, such as positron emission tomography (PET) [38]. Generally, the choice of the diagnostic test should be guided by the estimate of pre-test risk for coronary artery disease in women. For this reason, the score can be a useful tool. The WISE study group proposed a diagnostic flow-chart where coronary microvascular function must be associated with the estimation of ‘global risk’, for example using new markers to determine ‘atherosclerotic burden’, such as intima-media thickness, arterial reactivity, calcium score and perfusion at magnetic resonance imaging (MRI) (Fig. 2) [4].

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Figure 2 Proposed paradigm for testing of asymptomatic and symptomatic women including detection of subclinical and obstructive coronary disease. )6e20% for intermediate Framingham risk scores and 20% for high Framingham risk scores [4].

ECG exercise test Role in diagnosis One of the difficulties of detecting CHD in women is that the main diagnostic test is the exercise test, which is less sensitive and has lower diagnostic accuracy in women than in men [39] (Table 3). Despite its false-positive test results and important limitations, ECG exercise test is considered the initial test of election for CHD in women. Its use and indications for women are limited to those with a relatively normal 12-lead ECG, who are able to achieve moderate-to-high levels of exercise [4]. This poorer accuracy in women is related, in part, to the lower CHD prevalence as well as greater co-morbidity and functional impairment that preclude women from achieving maximum levels of exercise compared to more active men. Other reasons posited for a lower accuracy of the ECG in women include a lower QRS voltage and hormonal factors [4]. The accuracy of exercise testing in women may be enhanced by attention to features other than the absolute level of ST depression [40]. The exercise test provides a wealth of other material, including exercise capacity, haemodynamic response to exercise, and the presence of cardiac symptoms, which are used to interpret the test result. The accuracy of

exercise testing was significantly increased by the use of a multivariate model compared with ST-segment evaluation alone [41]. For both asymptomatic and symptomatic women, the choice of the initial test is guided by classifying women into low, intermediate or high pre-test risk categories. The American Guidelines recommend the ECG exercise test be performed on symptomatic women with intermediate risk who have a normal resting ECG and are capable of exercise [42]. As indicated in a recent Consensus, stress testing with exercise ECG or cardiac imaging has the greatest incremental value in symptomatic women with an intermediate to high pre-test probability of CHD. It remains controversial whether selective screening of asymptomatic women at intermediate risk for CAD should be routine. Current evidence does not support the use of imaging in low-risk asymptomatic women [43]. Role in prognosis Exercise stress test risk scores (e.g., Duke treadmill score) have been shown to improve prognostication in women but, of all the factors noted during testing, the strongest predictive parameter from the treadmill test is exercise duration. Exercise capacity is an independent predictor of death in asymptomatic women, to a greater extent than was previously established for men [44].

Table 3 Meta-analyses of diagnostic accuracy of exercise electrocardiography, stress echocardiography and stress SPECT imaging in women [4]. Exercise Electrocardiography

Stress Echocardiography

Author, Year (Ref.)

Sensitivity (%)

Specificity (%)

Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%)

Fleischmann et al., 1998 (143) Kwok et al, 1999 (146) Beattie et al., 2003 (143) Average

e 61 e 61

e 70 e 70

85 86 81 84

77 79 73 76

Stress SPECT

87 78 77 81

64 64 69 66

Coronary artery disease In one study, for each unit 1 metabolic equivalent (1 MET) increase in exercise capacity, there was a 17% reduction in mortality rate and the risk of death doubled for those in the 5- to 8-METs exercise capacity category and tripled for those in the lowest (5 MET) category when compared with the highest exercise capacity category, adjusted for the Framingham risk scores [44,45].

Stress echocardiography Role in diagnosis Evidence suggests that accurate risk assessment for CHD is possible with traditional testing including functional capacity, evaluation of extent and severity of myocardial perfusion defects by radionuclide techniques and stressinduced wall motion abnormalities on echocardiography [12]. Stress echocardiography, the most commonly applied test for wall motion assessment, has the advantages of a lower cost, absent radiation exposure and ability to image both cardiac structures and ventricular function. Despite these advantages, echocardiographic techniques can also be suboptimal in women due to obesity or lung disease, which limit acoustic windows and reduce exercise tolerance [4]. Women who are incapable of maximum exercise are commonly referred for dobutamine (in the US) or dipyridamole (in Europe) pharmacological stress echocardiography [46]. Stress echocardiography (either with exercise or with pharmacological stress) is an effective and highly accurate non-invasive tool for detecting CHD in women and provides incremental prognostic value over exercise ECG and clinical parameters in women with suspected or known coronary disease (i.e., Table 3, sensitivity 84% and specificity 76%).

Role in prognosis Stress echocardiography in women offers additional prognostic data: inducible wall motion abnormalities and global and regional left ventricular function are highly predictive of long-term outcome for women and men alike, whereas a normal study is associated with a low risk of cardiac events [47]. From a recent report on 4234 women, for exercising women the annual risk of dying is approximately 1 per 1000 if the results are negative and increases to 1 per 100 for those with high-risk ischaemia [48].

Single-photon emission computed tomography Role in diagnosis SPECT refers to the nuclear techniques which allow visualisation of global and regional perfusion defects, function and volumes of the ventricles. This method can improve diagnostic accuracy in women with coronary disease, but may give false positives due to the presence of breast tissue and because the heart is smaller in women than in men [20]. SPECT imaging has high diagnostic and prognostic accuracy in the evaluation of women with chest pain.

431

Role in prognosis A number of large observational studies have shown that myocardial perfusion SPECT imaging adds incremental prognostic value to clinical and exercise variables in women [43,49]. A normal stress SPECT study is associated with a ‘low risk’ for cardiac events (<1%/year risk of cardiac death or myocardial infarction) [50], whereas an abnormal perfusion study is associated with a worse prognosis [51]. In women undergoing exercise myocardial perfusion imaging, the number of abnormal territories remained the strongest correlate of mortality after adjustment for exercise variables [52]. When combined with clinical information, this examination allows risk stratification of diabetic patients [53]. Thus, diabetic women with a normal SPECT scan are at a higher risk than non-diabetic women, probably because diabetes causes important alterations in the regulation of coronary vasodilator function in both epicardial and resistance coronary vessels, functional abnormalities that precede the appearance of obstructive CHD [54].

Coronary artery calcium score (CACS) Role in diagnosis Computed tomography (CT) evaluates and quantifies the amount of calcium (early marker of coronary disease) in the coronary arteries. Coronary artery calcium score (CACS) is currently recognised as an independent and incremental predictor of events in patients at intermediate risk of CAD, and several guidelines support selective screening in these patients [55,56]. In a study of 539 women undergoing coronary angiography with a normal coronary tree, as many as 220 had coronary calcification with a negative predictive value of 100%. When the calcium score was between 100 and 400, women had a higher prevalence of stenosis [57]. Little data are available on calcium scores for risk stratification in asymptomatic women. A low or absent CACS may also prove useful in determining a low likelihood of developing CHD. Selected use of coronary calcium scores may be appropriate for patients with intermediate coronary disease risk [56]. In a recent study of patients (45% women) undergoing investigation of a chest pain syndrome, despite the high known negative predictive value of CACS for coronary events, a low and even 0 value of CACS did not exclude clinically important obstructive CHD in patients undergoing investigation of an acute or long-term chest pain syndrome. The authors concluded that, when possible, contrastenhanced multidetector computed tomography should be the non-invasive CT test of choice in these patients [58].

Role in prognosis CACS is an independent and complementary predictor of short- and long-term cardiac events. This screening method is equally accurate in stratifying risk in women and men. Relative risk of cardiovascular events increases proportionately to coronary calcium [59].

432 A recent study of 1126 asymptomatic patients (about 30% were women), demonstrated that a severe CACS identifies subjects at high long-term cardiac risk, even in the presence of a normal SPECT examination. The authors concluded that in patients who are at intermediate or high clinical risk of CAD, the use of CACS could better define those who will have a high long-term risk of adverse cardiac events [60].

Multi-slice computed tomography (MSCT) Role in diagnosis Multi-Slice Computed Tomography (MSCT) is a rapidly evolving coronary imaging technique, and a potential alternative to established non-invasive tests for CAD. The diagnostic accuracy of MSCT in women per se has not been investigated, rather it is extrapolated from reports on primarily male populations. Sensitivity for detecting significant coronary stenoses on a patient-by-patient analysis was 100%, specificity 75%, and positive and negative predictive values were 96% and 100% respectively. The 64slice computed tomography has a high-sensitivity for detecting significant coronary stenoses, and is reliable for excluding the presence of significant CAD in patients who present with a non-ST elevation ACS [61]. The sensitivity and negative predictive value for detecting significant CHD was very good, for both women and men, whereas there are conflicting data on diagnostic accuracy, specificity, and positive predictive value in women. One study demonstrated that these parameters were lower in women (probably because women have smaller vessels than men) [62], whilst another confirmed the high diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female patients [63]. Further studies are therefore needed to better validate this method in women.

Role in prognosis Data available on the prognostic utility of MSCT have shown that this test provides incremental prognostic information in patients with suspected but undocumented CAD: patients with one or more vessel obstructive CAD had increased hard events compared with those with less than one-vessel disease [64]. In patients with chest pain, the presence of moderate to severe coronary stenosis documented by MSCT are associated with a higher mortality risk than less extensive lesions, and a negative cardiac computed tomography angiography (CCTA) portends an extremely low risk for death. In these patients, MSCT may be a prognostically useful non-invasive imaging technique for the evaluation of patients with chest symptoms [65].

Cardiovascular magnetic resonance imaging (MRI)

C. Leuzzi, M.G. Modena contrast, three-dimensionality and overall superior temporal and spatial definition in imaging vascular and myocardial abnormalities [66]. Although not in common practice, MRI techniques have been applied for the evaluation of suspected myocardial ischaemia in female patients with chest pain symptoms and lower risk cohorts. MRI perfusion was reported to be highly accurate in detecting single-vessel obstructive CHD [67]. MRI delineates subendocardial perfusion (an initial manifestation of myocardial ischaemia) from epicardial perfusion and may provide corollary evidence as to the aetiology of chest pain symptoms in women, particularly in the absence of obstructive CHD [20]. In patients with syndrome X, cardiovascular MRI demonstrates subendocardial hypoperfusion during the intravenous administration of adenosine, which is associated with intense chest pain [66]. In addition, 31P MRI spectroscopy identifies alterations in high energy phosphates (i.e., reduction in phosphocreatine/ adenosine triphosphate (PCr/ATP) ratio) providing a direct assessment of metabolic myocardial ischaemia [68]. However, MRI has intrinsic limitations, with a closed bore magnet causing claustrophobia in certain patients.

Role in prognosis Knowledge on the prognostic value of stress MRI examinations is limited. One study demonstrated that in patients undergoing MRI cardiac stress tests for the detection of ischaemia, the presence of inducible ischaemia or a left ventricular ejection fraction (LVEF) <40% were associated with future myocardial infarction or cardiac death, regardless of the presence of conventional risk factors for coronary arteriosclerosis. Conversely, patients with no evidence of ischaemia and an LVEF of 40% had an excellent prognosis in the 2 years after stress cardiac MRI [69]. Another study confirmed these results, demonstrating that in patients with negative Adenosine stress magnetic resonance perfusion and dobutamine stress magnetic resonance, the 3-year event-free survival was 99.2% [70]. The prognostic utility of the dobutamine cardiac magnetic resonance stress test was also recently confirmed in women. In a similar way to men, the LV wall motion abnormalities inducible during dobutamine cardiac magnetic resonance predicted cardiac death and myocardial infarction in women. The authors concluded by saying that dobutamine cardiac magnetic resonance testing may be a valuable non-invasive stress imaging technique for identifying cardiac risk in women with known or suspected CHD [71]. Furthermore, women with a reduced PCr/ATP ratio and non-obstructive coronary arteries have worse event-free survival [68].

Conclusions Role in diagnosis MRI imaging may lend itself to the evaluation of women on account of its excellent soft tissue characterisation and

CHD is the leading cause of morbidity and mortality in women. There are marked gender differences in CHD symptoms, accuracy of diagnostic tests and outcomes

Coronary artery disease following intervention. Because women have been underrepresented in CHD clinical trials, further research involving larger female cohorts is required.

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