Utility of stress testing and coronary calcification measurement for detection of coronary artery disease in women

Accurate and safe diagnostic testing provides the crucial link between detection and optimal management of coronary artery disease (CAD). Noninvasive diagnostic testing for CAD may be less accurate in women than in men. Many noninvasive diagnostic modalities are available for this purpose. An exercise tolerance test provides an assessment of functional capacity and has the advantages of wide availability and low initial cost. However, exercise echocardiography may be the most cost-effective method for the initial assessment of coronary artery disease in intermediate-risk women owing to its higher sensitivity and specificity. Recent studies with electron-beam computed tomography reveal that women with no coronary calcification are very unlikely to have obstructive CAD. In symptomatic women with an intermediate likelihood of CAD, either an exercise treadmill test or exercise echocardiography is appropriate for initial screening and can provide useful prognostic information. Alternatively, an electron-beam computed tomographic scan with a 0 calcium score may spare many women with atypical chest pain or equivocal findings on an exercise tolerance test from undergoing more expensive stress imaging studies or coronary angiography. For high-risk symptomatic women, a more aggressive approach involving coronary angiography appears to be the preferred initial diagnostic strategy.     

Diagnosis and management of ischemic cardiomyopathy: Role of cardiovascular magnetic resonance imaging

Coronary artery disease (CAD) represents an important cause of mortality. Cardiovascular magnetic resonance (CMR) imaging evolved as an imaging modality that allows the assessment of myocardial function, perfusion, contractile reserve and extent of fibrosis in a single comprehensive exam. This review highlights the role of CMR in the differential diagnosis of acute chest pain by detecting the location of obstructive CAD or necrosis and identifying other conditions like stress cardiomyopathy or myocarditis that can present with acute chest pain. Besides, it underlines the prognostic implication of perfusion abnormalities in the setting of acute chest pain. Furthermore, the review addresses the role of CMR to detect significant CAD in patients with stable CAD. It elucidates the accuracy and clinical utility of CMR with respect to other imaging modalities like single-photon emission computed tomography and positron emission tomography. Besides, the prognostic value of CMR stress testing is discussed. Additionally, it summarizes the available CMR techniques to assess myocardial viability and describes algorithm to identify those patient who might profit from revascularization those who should be treated medically. Finally, future promising imaging techniques that will provide further insights into the fundamental disease processes in ischemic cardiomyopathy are discussed.     

Diagnostic value of coronary artery calcium scoring in low-intermediate risk patients evaluated in the emergency department for acute coronary syndrome

Early and accurate triage of patients with possible ischemic chest pain remains challenging in the emergency department because current risk stratification techniques have significant cost and limited availability. The aim of this study was to determine the diagnostic value of the coronary artery calcium score (CACS) for the detection of obstructive coronary artery disease (CAD) in low- to intermediate-risk patients evaluated in the emergency department for suspected acute coronary syndromes. A total of 225 patients presenting to the emergency department with acute chest pain and Thrombolysis In Myocardial Infarction (TIMI) scores <4 who underwent non-contrast- and contrast-enhanced coronary computed tomographic angiography were included. CACS was calculated from the noncontrast scan using the Agatston method. The prevalence of obstructive CAD (defined from the contrast scan as ≥ 50% maximal reduction in luminal diameter in any segment) was 9% and increased significantly with higher scores (p <0.01 for trend). CACS of 0 were observed in 133 patients (59%), of whom only 2 (1.5%) had obstructive CAD. The diagnostic accuracy of CACS to detect obstructive CAD was good, with an area under the receiver-operating characteristic curve of 0.88 and a negative predictive value of 99% for a CACS of 0. In a multivariate model, CACS was independently associated with obstructive CAD (odds ratio 7.01, p = 0.02) and provided additional diagnostic value over traditional CAD risk factors. In conclusion, CACS appears to be an effective initial tool for risk stratification of low- to intermediate-risk patients with possible acute coronary syndromes, on the basis of its high negative predictive value and additive diagnostic value.     

Stress echocardiography is superior to exercise ECG in the risk stratification of patients presenting with acute chest pain with negative Troponin.

OBJECTIVE: To compare exercise electrocardiography (ExECG) and stress echocardiography (SE) in the risk stratification of patients presenting to hospital with cardiac-sounding chest pain, non-diagnostic ECGs and negative cardiac Troponin. METHODS: Patients presenting with acute chest pain were prospectively randomised to early ExECG or SE. A post-test likelihood of CAD was determined by the pre-test likelihood and the result of the stress test. Patients with a low post-test likelihood of CAD were discharged; those with a high post-test probability were considered for coronary angiography. All others were managed according to standard hospital protocols. RESULTS: A total of 302 patients underwent either ExECG or SE. SE identified significantly more patients with a low post-test probability of CAD (80% vs 31%, p<0.0001) and significantly fewer patients with an intermediate post-test likelihood of CAD compared to ExECG (3% vs 47%; p<0.0001). Significantly fewer patients undergoing SE were referred for further tests to exclude or refute the diagnosis of CAD (16% vs 52%; p<0.0001). In total, 36 (12%) had flow limiting CAD demonstrated by coronary angiography. Significant CAD was seen in fewer patients with a positive ExECG than with a positive SE (56% vs 84% (p=0.12)). Event rates were low for both modalities in patients with low post-test probability (3.5% for SE vs 5.1% for ExECG; p=ns) though the number of patients identified as low risk was higher if SE was performed. CONCLUSION: Despite negative cardiac Troponin, 12% of patients with acute chest pain had significant CAD. SE is superior to ExECG in discriminating between those patients with a low and intermediate risk of CAD and correctly identified patients with significant CAD, as well as conferring an excellent prognosis in those considered low risk. SE significantly reduces the requirement for further tests to diagnose CAD compared to ExECG.     

Noninvasive Imaging for Patients with COVID-19 and Acute Chest Pain

Acute chest pain is a common presentation in patients with COVID-19. Although noninvasive cardiac imaging modalities continue to be important cornerstones of management, the pandemic has brought forth difficult and unprecedented challenges in the provision of timely care while ensuring the safety of patients and providers. Clinical practice has adapted to these challenges, with several recommendations and societal guidelines emerging on the appropriate use of imaging modalities. In this review, we summarize the current evidence base on the use of noninvasive cardiac imaging modalities in COVID-19 patients with acute chest pain, with a focus on acute coronary syndromes.     

Exercise echocardiography

Exercise echocardiography has been used for 30 years. It is now considered a consolidated technique for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Of the stress echocardiography techniques, it represents the first choice for patients who are able to exercise. Given that the cost-effectiveness and safety of stress echocardiography are higher than those of other imaging techniques, its use is likely to be expanded further. Recent research has also proposed this technique for the evaluation of cardiac pathology beyond CAD. Although the role of new technology is promising, the assessment of cardiac function relies on good quality black and white harmonic images.     

Evaluation of Non-ST Segment Elevation Acute Chest Pain Syndromes with a Novel Low-Profile Continuous Imaging Ultrasound Transducer

Background: This investigation was designed to test the hypothesis that continuous cardiac imaging using an ultrasound transducer developed in our laboratory (ContiScan) is superior to electrocardiogram (ECG) monitoring in the diagnosis of coronary artery disease (CAD) in patients with acute non-ST segment elevation chest pain syndromes. Methods: Seventy patients with intermediate to high probability of CAD who presented with typical anginal chest pain and no evidence of ST segment elevation on the ECG were studied. The 2.5-MHz transducer is spherical in its distal part mounted in an external housing to permit steering in 360 degrees. The transducer was placed at the left sternal border to image the left ventricular short-axis view and recorded on video tape at baseline, during and after episodes of chest pain. Two ECG leads were continuously monitored. The presence of CAD was confirmed by coronary arteriography or nuclear or echocardiographic stress testing. Results: Twenty-four patients had regional wall motion abnormalities (RWMA) on their initial echo which were unchanged during the period of monitoring. All had evidence of CAD. Twenty-eight patients had transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion throughout the monitoring period, 14 of these had no evidence of CAD, and four had evidence of CAD. These four patients did not have chest pain during monitoring. The sensitivity, specificity, and accuracy of echocardiographic monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%, and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was superior to ECG (P < 0.001). Conclusions: The data indicate that continuous cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in patients presenting with acute non-ST segment elevation chest pain syndromes. This technique could be a useful adjunct to ECG monitoring for myocardial ischemia in the acute care setting.     

The role of non-invasive imaging in the risk stratification of asymptomatic diabetic subjects.

AIMS: Coronary artery disease (CAD) is the leading cause of death in patients with diabetes. Patients often present with advanced and asymptomatic disease. Proposed strategies that may favourably affect CAD risk and outcomes in this patient population include identifying diabetic patients with subclinical disease at high risk of future cardiac events. The purpose of this article was to review the role of both atherosclerosis imaging tests (coronary calcium imaging and high-resolution ultrasound assessment of carotid intima-media thickness) and functional imaging techniques [stress echocardiography and radionuclide myocardial perfusion imaging (MPI)] in the diagnostic and prognostic evaluation of asymptomatic diabetic subjects. METHODS AND RESULTS: We identified studies using MEDLINE searches (1966 to April 2005) and by reviewing reference lists. A comprehensive list of search terms was applied. All stress echocardiography and MPI studies evaluating the prevalence and/or prognostic value of myocardial ischaemia (n = 19) and coronary calcium imaging studies (n = 2) evaluating the prognostic value of subclinical atherosclerosis in diabetic patients were included. CONCLUSION: Asymptomatic myocardial ischaemia can be detected in a significant proportion of diabetic subjects by non-invasive imaging tests such as MPI and stress echocardiography. The results of ongoing and future studies may be helpful in guiding the selection of asymptomatic diabetic subjects to undergo non-invasive imaging, establishing the cost-effectiveness of various testing strategies and their impact on prognosis.     

Coronary CT and the Coronary Calcium Score,the Future of ED Risk Stratification?

Accurate and efficient evaluation of acute chest pain remains clinically challenging because traditional diagnostic modalities have many limitations. Recent improvement in non-invasive imaging technologies could potentially improve both diagnostic efficiency and clinical outcomes of patients with acute chest pain while reducing unnecessary hospitalizations. However, there is still controversy regarding much of the evidence for these technologies. This article reviews the role of coronary artery calcium score and the coronary computed tomography in the assessment of individual coronary risk and their usefulness in the emergency department in facilitating appropriate disposition decisions. The evidence base and clinical applications for both techniques are also described, together with cost- effectiveness and radiation exposure considerations.     

Multi-slice computed tomography in the evaluation of patients with acute chest pain

Every year, a considerable number of patients present at the Emergency Department (ED) with acute chest pain complaints. In these patients, determining accurate diagnosis of acute coronary syndrome (ACS) remains clinically challenging. In general, triage is based on the initial clinical assessment including (stress) ECG and serial serum markers measurements. While management is relatively straightforward in case of ECG changes and elevated serum markers, a considerable number of patients presents with both serum markers and ECG that are either within normal limits or inconclusive. In these patients, non-invasive cardiac imaging has become an important tool in decision-making. Recently, non-invasive visualization of the coronary arteries has become possible with computed tomography (CT) techniques. Both electron beam CT (EBCT) and multi-slice CT (MSCT) allow assessment of coronary calcium burden as a marker of coronary artery disease (CAD). More recently, non-invasive coronary angiography can also be performed, for which MSCT in particular is increasingly used. Potentially these techniques could become useful in the clinical work-up of patients presenting with suspected ACS. The purpose of the present review is to discuss the potential roles of calcium scoring and non-invasive coronary angiography in patients presenting with suspected ACS.     

Comparison of the prognostic value of qualitative versus quantitative stress tomographic perfusion imaging

This study compared qualitative assessment of exercise thallium imaging to quantitative assessment in predicting outcome in 713 patients with 78% prevalence of coronary artery disease by coronary angiography; during a mean follow-up of 52 months, there were 106 hard cardiac events (death or nonfatal myocardial infarction). The qualitative method provided important prognostic information; however, unlike the quantitative technique, less patients were assigned to either the low- or high-risk group and proportionally more patients into the intermediate-risk group, which may limit the clinical usefulness of the technique.     

Complementary results of computed tomography and magnetic resonance imaging of the heart and coronary arteries: a review and future outlook

MR and CT imaging are emerging as promising complementary imaging modalities in the primary diagnosis of CAD and for the detection of subclinical atherosclerotic disease. For the detection or exclusion of significant CAD, both cardiac CT (including coronary calcium screening and non-invasive coronary angiography), and cardiac MRI (using stress function and stress perfusion imaging) are becoming widely available for routine clinical evaluation. Their high negative predictive value, especially when combining two or more of these modalities, allows the exclusion of significant CAD with high certainty, provided that patients are selected appropriately. The primary goal of current investigations using this combined imaging approach is to reduce the number of unnecessary diagnostic coronary catheterizations, and not to replace cardiac catheterization altogether. For the diagnosis of obstructive coronary atherosclerosis and for screening for subclinical disease, CT and MRI have shown potential to directly image the atherosclerotic lesion, measure atherosclerotic burden, and characterize the plaque components. The information obtained may be used to assess progression and regression of atherosclerosis and may open new areas for diagnosis, prevention, and treatment of coronary atherosclerosis. Further clinical investigation is needed to define the technical requirements for optimal imaging, develop accurate quantitative image analysis techniques, outline criteria for image interpretation, and define the clinical indications for both MR or CT imaging. Additional studies are also needed to address the cost effectiveness of such a combined approach versus other currently available imaging modalities.     

Women with high exercise tolerance and the role of myocardial perfusion imaging

BACKGROUND: Myocardial perfusion imaging (MPI) provides incremental diagnostic and prognostic information, even in patients with high exercise tolerance. HYPOTHESIS: Myocardial perfusion imaging provides significant diagnostic value, specifically in women with high exercise tolerance. METHODS: Our study population consisted of all women who underwent exercise MPI in our Department from January 1992 to June 1996 and reached at least Stage IV in the Bruce protocol. Patients were divided into those with known and those with possible coronary artery disease (CAD). All patients were followed for 3 years from the performance of MPI. RESULTS: Of 4,803 women who underwent myocardial perfusion imaging, 3,183 had exercise stressing, and of those, 311 reached at least Stage IV in the Bruce protocol. Of these 311 MPI scans, only 23 (7.4%) were abnormal (reversible, fixed, or mixed) and the remaining 288 (92.6%) were normal. Of the 82 patients with known CAD, 13 (15.8%) had an abnormal MPI, while only 10 (4.4%) of the 229 patients with possible CAD. No myocardial infarction or cardiac death occurred within 3 years; one patient with normal MPI needed revascularization. CONCLUSION: In women with high exercise tolerance, especially in those without already known CAD, the yield of MPI is very low. Women with high exercise tolerance have an excellent prognosis.     

Mitral valve prolapse in the ventriculogram: scintigraphic, electrocardiographic, and hemodynamic abnormalities

Patients with mitral valve prolapse (MVP) frequently have chest pain, which may be difficult to differentiate from angina pectoris in coronary artery disease (CAD). We performed resting and exercise ECGs, pulmonary arterial pressure measurements, radionuclide ventriculography (99mtechnetium), and perfusion scintigrams (201thallium) in 56 patients with angiographically proven MVP and no CAD. Pathological results were obtained in 31% of exercise ECGs, 33% of pulmonary arterial pressure measurements during exercise, 22% of radionuclide ventriculographies, and in 75% of thallium perfusion scintigrams. A significant correlation in pathological results was found only between exercise ECG and both radionuclide ventriculography and pulmonary arterial pressure measurements. Because of the high prevalence of false-positive perfusion scintigrams in patients with typical or atypical chest pain, the use of exercise 201Tl imaging as a screening method to separate patients with MVP from those with CAD will not be appropriate. The variability of cardiac abnormalities in our patients with MVP and angiographically normal coronary arteries suggests that the MVP syndrome may represent a variable combination of metabolic, ischemic, or myopathic disorders.     

Fractional Flow Reserve Derived from Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain: Rationale and Design of the FORECAST Trial

BackgroundFractional flow reserve measurement based on computed tomography (FFR_CT) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFR_CT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFR_CT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial.MethodsThe FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFR_CT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment.ConclusionThe FORECAST randomized trial will assess the clinical and economic outcomes of using FFR_CT as the primary test to evaluate patients presenting with stable chest pain.     

Left Coronary Artery Arteriovenous Malformation Presenting as a Diastolic Murmur with Exercise Intolerance in a Child with a Suspected Familial Vascular Malformation Syndrome

Objective. Intracardiac arteriovenous malformations are rare and may be associated with sudden death in adults. This case report describes an intracardiac left coronary arteriovenous malformation in a 7‐year‐old boy with a suspected familial cutaneous vascular malformation syndrome. The patient presented with a diastolic murmur, exercise intolerance, chest pain, and a left ventricular mass. Methods. The left ventricular mass was initially identified by echocardiography. Subsequently, a computed tomography scan revealed the vascular nature of the lesion. We hypothesized that the lesion represented either an arteriovenous malformation (AVM) or a hemangioma. These lesions are thought to cause coronary steal and myocardial dysfunction. Skin biopsies of the patient’s cutaneous lesions revealed capillary hyperplasia, which was not consistent with either hemangioma or AVM. Thus, a surgical biopsy and partial resection of the mass was performed. Results. The surgical pathology of the cardiac mass was consistent with an AVM. Within 6 months following partial resection of the mass, the patient unexpectedly developed a left ventricular pseudoaneurysm at the resection site and required re‐operation. Although a portion of the mass remains, both the patient’s chest pain and exercise tolerance have improved subjectively. Conclusion. Patients with cutaneous vascular malformations and diastolic murmurs, as well as cardiac symptoms, should undergo echocardiography or alternative imaging modalities to screen for treatable pathological myocardial vascular malformations.     

Isoproterenol infusion stress two-dimensional echocardiography in diagnosis of coronary artery disease in elderly patients. Comparison with the other stress testing methods

Since a dynamic exercise stress test cannot always be performed adequately in elderly patients, an alternative method is needed for evaluation of coronary reserve. We studied two-dimensional echocardiographic (2-DE) and electrocardiographic (ECG) responses to infusion of isoproterenol (ISP) at a rate of 0.02 micrograms/Kg/min in 40 elderly patients with chest pain. The results were compared with exercise ECG (EX-ECG) tests and exercise radionuclide angiocardiography (EX-RNA) in 13 of these patients. No serious complications were encountered in the ISP test. The diagnostic sensitivity for coronary artery disease (CAD) was 71% for ISP-2-DE, 71% for ISP-ECG, 86% for EX-ECG and 71% for EX-RNA. The specificity for CAD was 83% for ISP-2-DE, 33% for ISP-ECG, 50% for EX-ECG and 100% for EX-RNA. In conclusion, the ISP-2-DE test is a safe, easily available and useful method for the assessment of coronary artery disease in elderly patients.     

Can noninvasive exercise test criteria identify patients with left main or 3-vessel coronary disease after a first myocardial infarction?

This study attempts to determine whether exercise treadmill testing with clinical, electrocardiographic, and thallium-201 myocardial perfusion imaging data can identify which patients have left main or 3-vessel (anatomically high-risk) coronary artery disease (CAD) after their first transmural myocardial infarct (MI). Twelve exercise test criteria for high-risk disease were compared in 40 patients referred for cardiac catheterization; 34 had a history of chest pain and 17 had angiographically defined high-risk CAD. A thallium image defect outside the vascular distribution of the MI was the most reliable criterion to distinguish patients with high-risk CAD (p = 0.00052 for Fisher's exact test of discrimination). Thallium imaging was somewhat more sensitive (92 versus 65%, p = 0.108) when patients with negative thallium imaging criteria who failed to achieve 85% of the age-predicted maximal heart rate were excluded. Failure to achieve 85% of predicted heart rate was by itself a useful criterion for detecting high-risk CAD (p = 0.017), especially in patients not taking propranolol (p = 0.004). Development of positive S-T segment depression at less than 70% predicted heart rate also discriminated left main or 3-vessel disease from less extensive CAD (p = 0.016). Other criteria failed to discriminate significantly between high-risk and less extensive CAD in patients after their first MI (p greater than 0.05). S-T segment depression (p = 0.199) or chest pain (p = 0.577) during exercise testing were particularly unreliable. Further, none of the criteria for high-risk CAD were influenced by irreversible left ventricular dysfunction. It is concluded that patients with thallium imaging defects outside the region of the infarct, decreasing blood pressure during exercise, failure to achieve 85% of predicted heart rate, or S-T depression at less than 70% of predicted heart rate have a high probability of having left main or 3-vessel disease. Patients without these criteria have a very low probability of having high-risk CAD and probably do not need coronary angiography for the purpose of excluding these high-risk coronary lesions after a first MI.     

Myocardial Perfusion SPECT Imaging in Patients after Percutaneous Coronary Intervention

Coronary artery disease (CAD) is the most prevalent form of cardiovascular disease affecting about 13 million Americans, while more than one million percutaneous transluminal intervention (PCI) procedures are performed annually in the USA. The relative high occurrence of restenosis, despite stent implementation, seems to be the primary limitation of PCI. Over the last decades, single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), has proven an invaluable tool for the diagnosis of CAD and patients' risk stratification, providing useful information regarding the decision about revascularization and is well suited to assess patients after intervention. Information gained from post-intervention MPI is crucial to differentiate patients with angina from those with exo-cardiac chest pain syndromes, to assess peri-intervention myocardial damage, to predict-detect restenosis after PCI, to detect CAD progression in non-revascularized vessels, to evaluate the effects of intervention if required for occupational reasons and to evaluate patients' long-term prognosis. On the other hand, chest pain and exercise electrocardiography are largely unhelpful in identifying patients at risk after PCI.Although there are enough published data demonstrating the value of myocardial perfusion SPECT imaging in patients after PCI, there is still debate on whether or not these tests should be performed routinely.     

Non-invasive detection of vulnerable coronary plaque

Critical coronary stenosis have been shown to contribute to only a minority of acute coronary syndromes and sudden cardiac death.Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis.Consequently,a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease.Recent advances in invasive and non-invasive imaging techniques have shown the potential to identify these high-risk plaques.Non-invasive imaging with magnetic resonance imaging,computed tomography and positron emission tomography holds the potential to differentiate between low-and highrisk plaques.There have been significant technological advances in non-invasive imaging modalities,and the aim is to achieve a diagnostic sensitivity for these technologies similar to that of the invasive modalities.Molecular imaging with the use of novel targeted nanoparticles may help in detecting high-risk plaques that will ultimately cause acute myocardial infarction.Moreover,nanoparticle-based imaging may even provide non-invasive treatments for these plaques.However,at present none of these imaging modalities are able to detect vulnerable plaque nor have they been shown to definitively predict outcome.Further trials are needed to provide more information regarding the natural history of high-risk but non-flow-limiting plaque to establish patient specific targeted therapy and to refine plaque stabilizing strategies in the future.