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Purpose: Dynamic contrast enhanced MRI of the heart typically acquires 2-4 short-axis (SA) slices to detect and characterize coronary artery disease. This acquisition scheme is limited by incomplete coverage of the left ventricle. We studied the feasibility of using radial simultaneous multi-slice (SMS) technique to achieve SA, 2-chamber and/or 4-chamber long-axis (2CH LA and/or 4CH LA) coverage with and without electrocardiography (ECG) gating using a motion-robust reconstruction framework., Methods: 12 subjects were scanned at rest and/or stress, free breathing, with or without ECG gating. Multiple sets of radial SMS k-space were acquired within each cardiac cycle, and each SMS set sampled 3 parallel slices that were either SA, 2CH LA, or 4CH LA slices. The radial data was interpolated onto Cartesian space using an SMS GRAPPA operator gridding method. Self-gating and respiratory states binning of the data were done. The binning information as well as a pixel tracking spatiotemporal constrained reconstruction method were applied to obtain motion-robust image reconstructions. Reconstructions with and without the pixel tracking method were compared for signal-to-noise ratio and contrast-to-noise ratio., Results: Full coverage of the heart (at least 3 SA and 3 LA slices) during the first pass of contrast at every heartbeat was achieved by using the radial SMS acquisition. The proposed pixel tracking reconstruction improves the average SNR and CNR by 21% and 30% respectively, and reduces temporal blurring for both gated and ungated acquisitions., Conclusion: Acquiring simultaneous multi-slice SA, 2CH LA and/or 4CH LA myocardial perfusion images in every heartbeat is feasible in both gated and ungated acquisitions. This can add confidence when detecting and characterizing coronary artery disease by revealing ischemia in different views, and by providing apical coverage that is improved relative to SA slices alone. The proposed pixel tracking framework improves the reconstruction while adding little computational cost., Competing Interests: The authors have declared that no competing interests exist.

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

Unlabelled: The quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) using PET with (82)Rb in patients with known or suspected coronary artery disease has been demonstrated to have substantial prognostic and diagnostic value. However, multiple methods for estimation of an image-derived input function and several models for the nonlinear first-pass extraction of (82)Rb by myocardium have been used. We sought to compare the differences in these methods and models and their impact on prognostic assessment in a large clinical dataset., Methods: Consecutive patients (n = 2,783) underwent clinically indicated rest-stress myocardial perfusion PET with (82)Rb. The input function was derived using a region of interest (ROI) semiautomatically placed in the region of the mitral valve, factor analysis, and a hybrid method that creates an ROI from factor analysis. We used 5 commonly used extraction models for (82)Rb to estimate MBF and MFR. Pearson correlations, bias, and Cohen κ were computed for the various measures. The relationship between MFR/stress MBF and annual rate of cardiac mortality was estimated with spline fits using Poisson regression. Finally, incremental value was assessed with the net reclassification improvement using Cox proportional hazards regression., Results: Correlations between MFR or stress MBF measures made with the same input function derivation method were generally high, regardless of extraction model used (Pearson r > 0.90). However, correlations between measures derived with the ROI method and other methods were only moderate (Pearson r = 0.42-0.62). Importantly, substantial biases were seen for most combinations. We saw that the relationship between cardiac mortality and stress MBF was variable depending on the input function method and extraction model, whereas the relationship between MFR and risk was highly consistent. Net reclassification improvement was comparable for most methods and models for MFR but was highly variable for stress MBF., Conclusion: Although both stress MBF and MFR can improve prognostic assessment, MFR is substantially more consistent, regardless of choice of input function derivation method and extraction model used., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: The purpose of this study was to evaluate the predictive value of DM and resting HR on CAN in a large sample derived from a Chinese population., Materials and Methods: We conducted a large-scale, population-based, cross-sectional study to explore the relationships of CAN with DM and resting HR. A total of 387 subjects were diagnosed with CAN in our dataset. The associations of CAN with DM and resting HR were assessed by a multivariate logistic regression (MLR) analysis (using subjects without CAN as a reference group) after controlling for potential confounding factors. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the predictive performance of resting HR and DM., Results: A tendency toward increased CAN prevalence with increasing resting HR was reported (P for trend <0.001). MLR analysis showed that DM and resting HR were very significantly and independently associated with CAN (P < 0.001 for both). Resting HR alone or combined with DM (DM-HR) both strongly predicted CAN (AUC = 0.719, 95% CI 0.690-0.748 for resting HR and AUC = 0.738, 95% CI 0.710-0.766 for DM-HR)., Conclusion: Our findings signify that resting HR and DM-HR have a high value in predicting CAN in the general population.

Introduction and Objectives: The aim of this study was to determine the diagnostic value of using myocardial perfusion single-photon emission computed tomography (SPECT) with intravenous atropine administration at the end of submaximal exercise testing., Methods: One milligram of atropine was administered intravenously at the end of exercise testing to 172 patients who underwent a symptom-limited ergometric test but did not reach 80% of their peak heart rate without exhibiting angina or an ST-segment depression ≥1 mm. Within 1 week, 23 patients who satisfied scintigraphic criteria for ischemia during SPECT with atropine underwent SPECT for a second time without atropine administration with the aim of comparing the presence and severity of scintigraphic ischemia between the two studies (SDS: summed difference score)., Results: Of the 172 patients, 75 (43.6%) developed angina (n=56) or ST-segment depression (n=30) during atropine administration. Eight of the 23 patients (35%) who underwent two tests exhibited scintigraphic ischemia (SDS ≥2) on only the test with atropine. Furthermore, the SDS was significantly greater on SPECT imaging with atropine (5.6 ± 4.5 vs. 3.1 ± 2.8; P=.0001)., Conclusions: One-third of patients who met scintigraphic criteria for ischemia at the end of submaximal exercise testing and after atropine administration would not have met those criteria without administration of the drug.

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac radionuclide imaging (RNI) is frequently considered. This document is a revision of the original Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI) Appropriateness Criteria, published 4 years earlier, written to reflect changes in test utilization and new clinical data, and to clarify RNI use where omissions or lack of clarity existed in the original criteria. This is in keeping with the commitment to revise and refine appropriate use criteria (AUC) on a frequent basis. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Sixty-seven clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Additionally, use for perioperative testing was found to be inappropriate except for high selected groups of patients. It is anticipated that these results will have a significant impact on physician decision making, test performance, and reimbursement policy, and will help guide future research.

Background: Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR., Methods and Findings: We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%+/-18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8-2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5-51.1) and cardiac mortality (HR 17.4, 95% CI 2.2-137.4)., Conclusions: In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF., Trial Registration: Clinicaltrials.gov NCT00493168.

We present the case of a 43-year-old woman with a history of Ebstein's anomaly, who was referred for a myocardial perfusion single-photon emission computed tomography (SPECT) study due to angina-like symptoms. Dilatation of the right ventricle and right atrium, apical displacement of the septal tricuspid leaflet, small left ventricle with good left ventricular and a moderate degree of tricuspid regurgitation with mild pulmonary hypertension were found on echocardiography. Myocardial SPECT perfusion imaging with [99m Tc]tetrofosmin demonstrated a large defect in the inferior septal wall in the stress study with mild partial reversibility at rest. Coronary angiography revealed normal coronary arteries. Histological studies have shown that these patients develop increased fibrosis in the left ventricular wall and ventricular septum, especially in the basal and middle region of the septum, which adjoins with the atrialized component of the right ventricle. This is in concordance with the findings of the myocardial perfusion scan in the case described.

In the k-t sensitivity encoding (k-t SENSE) method spatiotemporal data correlations are exploited to accelerate data acquisition in dynamic MRI studies. The present study demonstrates the feasibility of applying k-t SENSE to contrast-enhanced myocardial perfusion MRI and using the speed-up to increase spatial resolution. At a net acceleration factor of 3.9 (k-t factor of 5 with 11 training profiles) accurate representations of dynamic signal intensity (SI) changes were achieved in computer simulations. In vivo, 5x k-t SENSE was compared with 2x SENSE (identical acquisition parameters except for in-plane spatial resolution = 1.48 x 1.48 mm(2) vs. 2.64 x 2.64 mm(2), respectively). In 10 volunteers no differences in myocardial SI profiles were found (relative peak enhancement = 151% vs. 149.7%, maximal upslope = 12.9%/s vs. 13.3%/s for 2x SENSE and 5x k-t SENSE, respectively, all P > 0.05). Overall image quality was similar, but endocardial dark rim artifacts were reduced with k-t SENSE. Signal-to-noise ratio (SNR) in the myocardium was greater with 5x k-t SENSE by a factor of 1.36 +/- 0.23 at peak contrast enhancement with the relative yield decreasing with increasing dynamics in the object in accordance to theory. Higher nominal acceleration factors of up to 10-fold were shown to be feasible in computer simulations and in vivo.

Whether coronary artery calcium (CAC) screening in pretransplant patients may help predict silent myocardial ischemia is unknown. Accordingly, we performed CAC imaging on 46 nondiabetic patients awaiting kidneytransplant. All patients underwent multidetector computed tomography imaging for CAC quantification, and a vasodilator myocardial perfusion stress (MPS) test was performed only in patients with a total CAC score>300 or>100 in a single coronary artery. The mean patient's age was 46+/-14 years and the median dialysis vintage was 33 months (interquartile range 19-53). The median CAC score was 82 (interquartile range 0-700) and correlated with patients' age (p=0.006) and dialysis vintage (p=0.02). Nineteen patients qualified for MPS, but 5 refused the test. Of the remaining 14 patients, 7 patients had normal scans and 7 showed a minimal perfusion defect in the inferoposterior segment of the left ventricle. At the time of writing, 12 patients have undergone successful kidney transplantation without untoward complications. CAC screening does not appear to be associated with silent ischemia in pretransplant patients. Though CAC is extensive in dialysis patients, calcium may be associated with nonobstructive atherosclerotic lesions or calcification of the media layer of the vessel wall.

The Electron Beam CT (EBT) Coronary Calcium Score (CCS) is an independent predictor of coronary events and adds incremental information to standard risk factors. How to use this information was uncertain. To assist our referring physicians in utilizing this test, a web based calculator was created that combines the Framingham score risk with the EBT CCS risk to obtain a new risk for cardiac events. To create this calculator, CCS breakpoints of 0, 80, 400, and 600 were selected; and from these breakpoints, 5 ranges of calcium scores: 0, 1-80, 81-400, 401-600, and >600 were defined. Bayes theorem was used to derive equations for the combined Framingham score risk and calcium score range risk for each CCS range. The sensitivity and specificity of each of these CCS breakpoints for the prediction of events was derived from prospective studies. These equations were then translated into a JavaScript program that could be accessed from a web browser. This calculator can be easily used to restratify many individuals classified as low, intermediate, or even high risk according to the Framingham risk score system into a different risk group, allowing more appropriate matching of intervention intensity with absolute cardiovascular event risk.

Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.5 and 3.5 mg /m3 for 6 h/d for 3 d. Radiotelemetry recordings of electrocardiogram (ECG) were analyzed for changes in T-wave morphology (QT interval, T-wave amplitude, and T-wave Area). Following exposures, lung lavage and blood samples were obtained to assay for markers of pulmonary and systemic inflammation. No exposure induced significant changes in heart rate and only the high concentration of road dust induced signs of pulmonary inflammation. T-wave area exhibited significant deviation from baseline values during exposure to gasoline exhaust particulates, but not to either concentration of road dust or gasoline emissions sans particulates. Gasoline-exposed mice demonstrated elevated plasma endothelin-1, but did not cause systemic inflammation. These data support the hypothesis that freshly-generated engine emissions, as opposed to resuspended paved road dust, may drive cardiac effects that have been observed at road-sides in the environment. The absence of ECG effects for both very high concentrations of road dust PM and equivalent concentrations of the vapor/gas phase of gasoline engine exhaust further indicate the specific risk conferred by fresh vehicular PM.

This study sought to validate different software applications for cardiac function analysis using ECG-gated CT and MR datasets in correlation with underlying heart rate. Ten patients and a set of ventricular phantoms underwent concurrent multislice-CT and cine-MR imaging for evaluation of cardiac function. Datasets from both imaging modalities were evaluated utilizing 2 volumetric analysis tools to determine left ventricular volume and mass. Initially, intraobserver measurement variability was assessed. Detected measurement variability was correlated with underlying absolute magnitude of cardiac volumes and masses. Subsequently, results were statistically evaluated by determining significant data variability depending on imaging modality and choice of evaluation software. Finally, the data variability was correlated with underlying heart rates. This study showed that all analyzed datasets uniformly presented intraobserver variations below 2%, and variability was not related to the magnitude of measurement. Significant measurement accuracy was proven in all calculated parameters obtained from the cardiac phantoms. Acquired patient datasets and calculated functional parameters showed significant data homogeneity, with measurement variability coefficients ranging from 0.935-0.955. CT datasets showed maximal data variability at heart rates below 60 BpM. MR datasets showed maximal data variability at heart rates above 90 BpM. In conclusion, CT and MR datasets allowed an interchangeable utilization of volumetric analysis tools. However, reliable volumetric analysis was limited to an optimal range of cardiac rates for each modality, thus emphasizing the necessity of reporting volumetric measurement results in combination with heart rate to allow for consideration of this possible cause for measurement variation.

Electrocardiographically gated myocardial perfusion SPECT (GSPECT) is a state-of-the-art technique for the combined evaluation of myocardial perfusion and left ventricular function within a single study. It is currently one of the most commonly performed cardiology procedures in a nuclear medicine department. Automation of the image processing and quantification has made this technique highly reproducible, practical, and user friendly in the clinical setting. In patients with coronary artery disease, gating enhances the diagnostic and prognostic capability of myocardial perfusion imaging, provides incremental information over the perfusion data, and has shown potentials for myocardial viability assessment and sequential follow-up after therapy. After reading this article, the readers will understand (a) the general principles of GSPECT and quantitation, (b) the methods of the image acquisition and analysis, (c) validation of GSPECT with other cardiac imaging modalities, and (d) application of the GSPECT-derived functional parameters in the clinical practice.

In severe coronary artery disease (CAD), it has been shown that intramyocardial inotropic reserve as assessed with tagged magnetic resonance imaging (MRI) is uniformly distributed among positron emission tomography (PET) patterns reflecting normal or concomitant reductions in perfusion and glucose metabolism. This preliminary study aimed to delineate the relationship between preoperative values of intramyocardial inotropic reserve (in different PET patterns of perfusion and glucose uptake) and intramyocardial functional outcome after surgical revascularization in severe CAD. Twelve patients underwent preoperative tagged MRI (baseline, 10 microg.kg(-1).min(-1) of dobutamine), H2 15O/[18F]fluorodeoxyglucose PET imaging, and postoperative resting tagged MRI. Regional midmyocardial circumferential shortening (Ecc, in %) and PET patterns (normal, match viable, mismatch viable, and infarcted) were assessed in three tagged MRI/PET short-axis slices. Ecc at baseline ranged from 12 +/- 6 to 8 +/- 5 and 4 +/- 4% in normal, match-viable, and infarcted regions, respectively (P <0.05) and was 8 +/- 5% in mismatch-viable regions. Of the 429 regions studied, 187 showed preoperative inotropic reserve with dobutamine, but 238 showed postoperative functional improvement. Postoperative functional improvement was less common in infarcted regions (41 vs. approximately 60% in the other PET patterns), but the extent of improvement was similar among PET patterns (approximately 6%). Postoperative functional improvement occurred in 53% of all (normal, match viable, and mismatch viable) regions without inotropic reserve. In severe CAD, revascularization affords greater intramyocardial functional benefit than expected from the evaluation of intramyocardial inotropic reserve with low-dose dobutamine. Postoperative functional improvement in PET-viable regions without inotropic reserve suggests that factors other than regionally enhanced perfusion contribute to such functional improvement.

Purpose: To compare the visual analysis of magnetic resonance imaging (MRI) with the tagging technique and Doppler tissue echocardiography with invasive ventriculography in detecting and quantifying regional left ventricular wall motion abnormalities., Materials and Methods: Sixteen patients with coronary artery disease and a history of prior myocardial infarction underwent invasive ventriculography, Doppler tissue echocardiography and MR-tagging within one week. Regional wall motion abnormalities (WMA) were detected in all patients. WMA were graded as normal = 1; hypokinetic = 2; akinetic = 3; or dyskinetic = 4. For agreement between MRI, echocardiography, and ventriculography the kappa coefficient (kappa) according to Cohen was calculated., Results: The kappa coefficient (kappa) was 0.962 for agreement between MRI and echocardiography and 0.602 for agreement between MRI and ventriculography as well as between echocardiography and ventriculography., Conclusion: Reliable analysis of regional left ventricular wall motion abnormalities is feasible using visual analysis of MR-tagging. MRI and Doppler tissue echocardiography detect more WMA than invasive ventriculography and grade them as more severe.

Unlabelled: Clinical decisions regarding diagnosis and effective treatment of coronary artery disease frequently require integration of information from various imaging modalities, which are acquired, processed, and read at different physical locations and times. We have developed methods to integrate the information in 2 cardiac imaging studies, perfusion SPECT and coronary angiography. Three-dimensional (3D) models of the coronary artery tree created from biplane angiograms were automatically aligned with 3D models of the left ventricular epicardial surface created from perfusion SPECT. Myocardial mass at risk was used as a unique measure to validate the accuracy of the unification., Methods: Thirty patients were injected with the perfusion agent (99m)Tc-tetrosfosmin during balloon occlusion while undergoing percutaneous transluminal coronary angioplasty for single-vessel coronary artery disease. Thus, a single, severe perfusion defect was induced by a single coronary artery occlusion of known severity and placement. The accuracy of the unification was measured by computing the overlap between physiologic area at risk, determined using SPECT perfusion quantification techniques only, and anatomic area at risk, determined using coronary artery anatomy aligned with the epicardial surface of the left ventricle., Results: The unification resulted in an 80% overlap of areas at risk, and an overlap of 84% of normal areas, for all coronary artery distributions. The mass at risk measured based on the unified anatomic information correlated with the physiologically based mass at risk as y = 0.92x + 10.3 g; r = 0.76, SEE = 10.4 g., Conclusion: A unification algorithm for automatically registering 3D models of the epicardial surface from perfusion SPECT and 3D coronary artery trees from coronary angiography has been presented and validated in 30 patient studies.

Patients complaining of chest pain (CP) who visit the emergency department (ED) represent the second cause of consultation in this department, and 20-30% of hospital admissions for medical reasons. These patients form a somewhat heterogeneous group with many different aetiologies and degrees of severity. In this setting, the clinical objectives include the prompt identification of patients with acute coronary syndromes (ACSs), the prompt evaluation of the immediate risk (i.e., initial risk stratification) of cardiovascular complications in order to tailor the treatment for each individual patient and to make the best use of hospital resources, and the prompt identification of patients with other potentially severe diseases. The diagnosis of ACS in patients coming to the ED for CP or any equivalent angina is one of the most difficult diagnostic challenges facing physicians in the ED. The correct diagnosis and risk stratification of these patients has clinical consequences, as well as very important legal and economic implications. The only methodology with a clear clinical impact on diagnosis, risk stratification and initial management is clinical evaluation based on data obtained by questioning the patient, carrying out a physical examination, and interpreting the results of a standard 12-lead electrocardiogram (ECG). Nevertheless, its combined diagnostic efficiency for ACS is imperfect and additional strategies are emerging which include serial ECG, the detection of serum biochemical markers of myocardial necrosis, exercise testing, and radionuclide myocardial perfusion imaging.

The assessment and appropriate clinical management of patients with acute chest pain and non-diagnostic electrocardiograms remain a continuing clinical problem. Accordingly, there is considerable interest in evaluating new strategies to improve early diagnostic accuracy in patients with possible acute myocardial ischaemia. Cardiac troponins (T and I) and acute rest myocardial perfusion imaging have similar sensitivities for detecting acute myocardial infarction. Whereas cardiac markers require 6-12 h to become positive, acute rest myocardial perfusion imaging immediately reflects the status of regional myocardial blood flow at the time of radiopharmaceutical injection. The measurement of cardiac troponins is particularly useful in the diagnosis and estimation of the degree of myocardial injury in those patients with a high likelihood of coronary artery disease and myocardial necrosis and for prognostication of adverse cardiac events in those patients with unstable angina. In contrast, the most appropriate use of acute rest myocardial perfusion imaging is in the setting of patients with acute ischaemic symptoms, non-diagnostic electrocardiogram and a low likelihood of myocardial necrosis, in which early imaging will assist in effective triage decisions.

Unlabelled: Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing (CPT) with that of dipyridamole, a pharmacologic vasodilator, on coronary blood flow (CBF) measured by PET in NIDDM patients and healthy volunteers. In addition, we studied the effect of acute angiotensin-converting enzyme (ACE) inhibition on the flow response., Methods: Ten NIDDM patients and 10 control subjects participated. Myocardial perfusion was determined at baseline, during CPT, and after dipyridamole infusion by PET using intravenous (13)N-ammonia., Results: Resting CBF was similar in NIDDM patients and in control subjects. CPT increased CBF by 20% in the control group, whereas no increase was observed in the patients. After dipyridamole infusion, CBF increased 2- to 3-fold in patients and 3- to 4-fold in control subjects. The increase and maximal CBF were significantly higher in control subjects than in patients. During ACE-inhibitor infusion, which had no influence on resting CBF in patients or control subjects (n = 5), CPT increased CBF by 14% in the NIDDM group. After dipyridamole, CBF increased 3- to 4-fold in both groups. The increase in CBF and maximal CBF in the 2 groups were not different during ACE-inhibitor infusion., Conclusion: In these NIDDM patients without evidence of epicardial coronary disease, endothelial dysfunction is strongly suggested by an impaired increase in CBF both to dipyridamole and to CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE inhibition during CPT did induce significant increases in CBF in the patients, the changes during ACE inhibition were small compared with the dipyridamole response, and the absence of CBF increase during CPT in 3 of the 10 control subjects further limits the value of CPT for the study of coronary endothelial dysfunction.

Objective: To evaluate the feasibility, safety and diagnostic accuracy of pharmacologic stress of (99m)Technetium-MIBI single-photon emission computed tomography (SPECT) with intravenous adenosine triphosphate (ATP) in patients with suspected coronary artery disease., Methods: The study group included 263 patients who were suspected of having coronary artery disease. All patients underwent (99m)Tc-MIBI myocardial perfusion imaging with ATP infusion (0.16 mg/kg body weight per min for 5 min). 20 mCi of (99m)Tc-MIBI were injected 3 minutes after the start of ATP infusion. Myocardial SPECT images were obtained 60 minutes later. Then, two days later, 20 mCi of (99m)Tc-MIBI were administered at rest and myocardial SPECT was repeated. 51 patients also underwent coronary angiography within two weeks for evaluation of sensitivity and specificity of ATP-myocardial perfusion imaging in detection of coronary artery disease. The occurrence of cardiac and non-cardiac adverse effects was carefully monitored during and after intravenous ATP infusion., Results: The ATP infusion protocol was completed in all patients. Although 59% of the patients had various kinds of adverse effects, most of them were mild. No patient required aminophyline. The most severe adverse effect was second degree type II atria-ventricular block (4/263), but all events were transient. The sensitivity and specificity of ATP-myocardial perfusion imaging were 97% and 82%, respectively., Conclusions: It is shown that (99m)Technetium-MIBI SPECT with intravenous ATP is a safe and feasible technique for detecting coronary artery disease in patients unable to perform the exercise test.

Background: Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutamine echocardiography (DbE)., Methods: Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter., Results: Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P <.0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P <.0001). Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P =.0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress., Conclusion: Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

Myocardial blood flow (MBF) can be quantified using dynamic T1-weighted MRI of diffusible tracers and a mathematical model of underlying vasculature. Quantification of MBF by means of T1- weighted MRI requires knowledge of the arterial input function (AIF). The AIF can be estimated from the left ventricular (LV) cavity. However, dispersion may occur between the LV and the tissue of interest because of the laminar blood flow profiles, branching of venules, and because of stenosis. To evaluate the influence of dispersion on the results of MBF quantification, a simulation study was performed. The dispersion was described as a convolution of the AIF with an exponential residue function. Synthetic tissue and AIF curves were analyzed and the derived parameters fit to the simulated parameters. The results show that an unaccounted dispersion may result in a systematic underestimation of MBF up to approximately 50%. Underestimation increases with increasing dispersion and with increasing MBF. Assuming equal dispersion at rest and during hyperemia, myocardial perfusion reserve (MPR) estimates are also susceptible to underestimation of approximately 20%. An unaccounted dispersion therefore can lead to systematic underestimation of both blood flow and perfusion reserve., (Copyright 2002 Wiley-Liss, Inc.)

Background: There is scanty information on the angiographic and myocardial perfusion correlates of dobutamine-induced ST-segment elevation., Methods and Results: We studied 39 patients who exhibited ST-segment elevation during dobutamine perfusion tomography and had recent coronary angiography performed (ie, within 3 months of the dobutamine study). Baseline characteristics, extent of coronary artery disease, relationship of Q waves to ST-segment elevation, ischemic burden, and angiographic findings were assessed. Twenty-nine patients (74%) had prior myocardial infarction, and 77% had abnormal Q waves at baseline. Ninety-three percent of patients had abnormal perfusion imaging. Eighty percent of patients had multivessel coronary artery disease. The left ventricular ejection fraction by contrast ventriculography was 35% +/- 7% (mean +/- SD), the perfusion defect size was 32% +/- 15%, and 73% of patients had some degree of myocardial ischemia. A predominance of ischemia (>50% reversibility) occurred in 38% of patients with Q waves and in 70% of those without Q waves. There was also good agreement between the site of ST-segment elevation and the site of ischemia by perfusion imaging (79%) and between the site of ST-segment elevation and the location of the vessel with significant coronary stenosis (95%)., Conclusions: Patients with dobutamine-induced ST-segment elevation have a depressed left ventricular ejection fraction, a high frequency of multivessel disease, and markedly abnormal myocardial perfusion tomography. In patients with ST-segment elevation and abnormal Q waves, substantial scarring and superimposed ischemia coexist, whereas in patients without Q waves, ST-segment elevation usually denotes severe ischemia.

Background: Our objective was to study the differences in relative count distributions in the left ventricular walls with attenuation compensation (AC) versus AC and triple-energy-window scatter compensation (SC), compared with standard filtered backprojection (FBP)., Methods and Results: Two hundred patients identified as having normal cardiac perfusion with FBP after undergoing either pharmacologically or physiologically induced stress were included in this study. Projection data were reconstructed with FBP, 10 iterations of ordered-subset expectation-maximization (OSEM) with AC, and OSEM with AC+SC. A comparison was made of average percentage of maximum counts within each of 9 regions of CEqual (Marconi Medical Systems, Inc, Cleveland, Ohio) polar maps (ie, the apex, 4 midventricular regions, and 4 basal regions). Compared with OSEM(AC), a slight decrease at the apex exists when SC is included. The elevated inferior-to-anterior count ratio in the midventricular and basal regions noted with OSEM(AC) decreased to close to 1.0 with OSEM(AC+SC). The anterior-to-lateral ratio for both regions was closest to 1.0 for OSEM(AC+SC). In the midventricular region, the lateral-to-septal ratio decreased further below 1.0 with OSEM(AC+SC) than it did with OSEM(AC). This was the only basal ratio not to improve to close to 1.0 with OSEM(AC+SC). In a subset of patients identified at the time of clinical reading as having a possible attenuation-caused decrease in the inferior region, AC elevated the inferior-to-anterior ratio to above 1.0 for the midventricular region. AC+SC resulted in a ratio of near 1.0 for this region. In another subset of patients identified as having anterior attenuation artifacts, compensation methods (either AC or AC+SC) failed to show an improvement compared with FBP., Conclusions: AC and SC improve the uniformity of the polar map, especially by bringing the inferior-to-anterior ratio closer to 1.0. Further investigation is necessary to determine the cause of the increased midventricular septal polar map count. In addition, the subset of patients identified as having breast-like attenuation artifacts causing a decreased polar map count in the anterior wall (relative to the inferior wall) also needs further attention.

There are between 3 and 5 million visits to EDs each year for complaints of chest pain. Of these, about one half of the patients have a noncardiac cause for their chest pain. Of the remainder, about 30% to 50% have significant coronary disease. It is quite clear that patients who are at high risk for a coronary event should be admitted to the hospital. For the low-to-moderate risk patients, the decision to admit or discharge the patient from the ED is not quite so easy. The emergency physician has to decide which tests can be helpful in the decision-making process, this can be undertaken in conjunction with a consultative cardiologist. It can be argued that if a patient does not have a normal test result whichever that evaluatory test is), then the patient should be admitted for further work-up and evaluation. The easiest test to perform in the ED setting is an echocardiogram. The images can be sent by telecommunication to a qualified echocardiogram reader for interpretation. This also has a reasonable NPV, although not necessarily as good as some of the other modalities available, unless interpreted in light of cardiac enzyme test results. If the index of suspicion is still high, then a stress echocardiogram can be considered. This has an excellent NPV and can be easily performed in [table: see text] most patients. This should not be undertaken in the face of an evolving MI, and patients should be observed for at least 8 hours after their initial presentation to the ED prior to undergoing a provocative test. Nuclear scintigraphy, another modality available for cardiac risk stratification, can be a logistical nightmare. The nuclear isotopes are strictly regulated by the Nuclear Regulatory Commission. The emergency physician may inject the isotopes, provided that he or she has undergone the necessary radiation training. Also, the patient must be removed from the ED to a radioisotope-approved area for the duration of the scan. One of the most difficult questions left open after review of all these analytical modalities is the duration of time these test results remain valid; when does an individual patient need to be reevaluated as to their specific pretest probability? The answer to this question lies in the presenting clinical scenario. If the patient presents with a similar inciting trigger for his or her symptoms, and the cardiac risk profile has not changed appreciably, then the previous study (whether a provocative stress test or even a cardiac catheterization) probably can be reliably counted. If the patient's risk profile has changed or the symptoms are new or more intense, the physician is compelled to pursue this encounter as a new, acute event. This can be true even in the setting of a previous cardiac catheterization that showed nonobstructive coronary disease, because plaque rupture can be acute and unpredictable. Ultimately, optimal care calls for each institution to develop a specific approach, in conjunction with their consultative cardiologist or critical care specialist, to enhance patient care, safety, and diagnostic outcome, while maintaining cost efficiency.

Background: Increased lung uptake during exercise thallium 201 single photon emission computed tomography is related to left ventricular dysfunction and extent of coronary artery disease (CAD). We studied the influence of the lung region of interest (ROI), used to quantify Tl-201 lung uptake, on the diagnostic value of the lung-to-heart uptake ratio (LHR) in detecting CAD with Tl-201 myocardial single photon emission computed tomography., Methods and Results: We retrospectively studied 152 consecutive patients referred to our center for stress Tl-201 scanning. Of these, 116 had proven multivessel CAD and 36 had either normal findings on coronary angiogram or a low likelihood (<5%) of CAD. Poststress quantitative analysis was performed from a 4 x 4-pixel ROI over the hottest myocardial region, an 8 x 8-pixel left lung ROI, an 8 x 8-pixel right lung ROI, and a manual ROI encompassing the whole right lung. The LHR was calculated for each lung ROI. Right LHR (R-LHR) provided the best interobserver and intraobserver reproducibility. R-LHR and total R-LHR values were significantly higher in patients with CAD. Only history of myocardial infarction significantly influenced the R-LHR measurement., Conclusions: The methodology of LHR measurement significantly influences the clinical contribution of Tl-201 lung uptake evaluation. Optimal reproducibility and diagnostic accuracy are provided by a right lung ROI.

Background: A profound autonomic unbalance is present in heart failure: its correlation with the etiology of the disease has never been investigated., Aims: We characterized the sympatho-vagal balance and autonomic responsiveness of 42 patients (21 with ischemic heart failure, 21 with idiopathic dilated cardiomyopathy). Patients had comparable NYHA class, ejection fraction, exercise pVO(2), exercise ventilatory response, incidence of beta-blocking treatment. None showed periodic breathing or nocturnal arterial desaturation., Methods: Heart rate variability was assessed in the time and frequency domain during: (1) 10 min of quiet supine resting and free breathing; (2) 10 min of regular breathing at a frequency of 20 acts/min (=parasympathetic stimulus); and (3) 10 min of active standing (=sympathetic stimulus). The ratio of the low- to high-frequency components of each autospectrum obtained in the frequency domain (LF/HF) was used as an index of sympathovagal balance., Results: Patients with ischemic heart failure had a greater baseline sympathetic activation (higher LF/HF) than those with idiopathic dilated cardiomyopathy, maintaining some parasympathetic responsiveness as well (reduced LF/HF with regular breathing)., Conclusions: There is a distinct autonomic control according to the etiology of heart failure, a finding that may help understanding its pathophysiology, and could be useful in the clinical management of patients.

Noninvasive assessment of regional myocardial perfusion is clinically important for early and accurate diagnosis of coronary artery disease. In addition, persistent metabolic alterations are often seen in post ischemic dysfunction after recovery of blood flow. Thus, prior ischemic insult may be identified as areas of altered metabolism despite normal perfusion (so-called ischemic memory imaging). Radionuclide imaging has great advantages over other imaging techniques based on the variety of radiopharmaceutical agents to probe regional cellular functions and biochemistry in vivo. Technetium-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with electrocardiogram-gated acquisition. Positron emission tomography (PET) enables metabolic assessment in vivo. Preserved fluorodeoxyglucose (FDG) uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently, iodine-123 15-(p-iodophenyl)-3R, S-methyl pentadecanoic acid (BMIPP), a branched fatty acid analog, has become clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. This perfusion metabolic mismatch, which is also observed by FDG-PET, is identified with stunned or hibernating myocardium with regional dysfunction. Both are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting use as an ischemic memory imaging. These new techniques will provide insights into new pathological states in ischemic heart disease and help to select the optimal treatment for the patients.

Background: Prior angiographic study has shown that the patterns of ST-segment depression during exercise do not provide localizing information of the responsible coronary lesion. However, little is known regarding the ability of exercise-induced ST-segment displacement to localize myocardial perfusion defects., Methods and Results: We studied 552 consecutive patients without prior myocardial infarction who had reversible perfusion defect in one vascular territory on rest 201Tl/exercise 99mTc-labeled sestamibi dual-isotope myocardial perfusion single photon emission computed tomography (SPECT) and ischemic ST depression or elevation during exercise. Of these, 192 patients had angiographically documented coronary artery disease (CAD). Two hundred thirty-two patients had maximal ST depression in anterior leads, 247 patients had maximal ST depression in inferior leads, and 45 patients had similar maximal ST depression in both anterior and inferior leads. Twenty-eight (5%) patients had ST elevation with absent Q waves. In patients with maximal ST depression in anterior leads, perfusion defects were found in the territory of the left anterior descending coronary artery (LAD) in 30%, in the territory of the right coronary artery (RCA) in 52%, and in the territory of the left circumflex coronary artery (LCX) in 18%. In patients with maximal ST depression in inferior leads, perfusion defects were found in RCA territory in 44%, in the LAD territory in 42%, and in the LCX territory in 14%. Compared with exercise ST depression, the less common finding of ST elevation did provide accurate localization of perfusion defects. When ST elevation was greatest in the anterior leads, 96% of patients had LAD territory defects. When ST elevation was most prominent in the inferior leads, 100% patients had RCA territory defects. Data of coronary angiograms demonstrated that myocardial perfusion SPECT correctly identified the most stenotic coronary disease for LAD (94%), LCX (72%), and RCA (75%)., Conclusions: The findings of this study indicate that the site of maximal ST-segment depression does not identify the localization of myocardial perfusion defects. However, the less common finding of exercise-induced ST-segment elevation does predict localization of myocardial ischemia.

In recent years, evaluation of cardiac autonomic activity by means of heart rate variability (HRV) determination and baroreflex sensitivity (BRS) testing has become readily available. The results of the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study showed that both diminished HRV and baro-reflex sensitivity are associated with poor outcome in patients after myocardial infarction. In contrast to patients with coronary disease little information is available concerning cardiac autonomic activity in idiopathic dilated cardiomyopathy (IDC). Therefore, HRV and BRS were assessed in 160 patients with IDC and preserved sinus rhythm in order to investigate the relationship between HRV, BRS, and left ventricular ejection fraction. Time domain indices of HRV were computed from 24-hour digital Holter recordings. BRS testing was performed using the noninvasive phenylephrine method. Mean standard deviation of all normal RR intervals (SDNN) of the whole study population was 112 +/- 46 ms. A well preserved HRV (SDNN > 105 ms) was found in 74 patients (46%), a moderately decreased HRV (SDNN 70-105 ms) in 59 patients (37%), and a severely decreased HRV (SDNN < 70 ms) in 27 patients (17%). Mean BRS was 7.5 +/- 5.0 ms/mm Hg. A well preserved BRS (> 6 ms/mm Hg) was present in 78 patients (57%), a moderately decreased BRS (3-6 ms/mm Hg) was present in 38 patients (28%), and a severely decreased BRS (< 3 ms/mm Hg) in 21 patients (15%). There was only a weak correlation between SDNN and BRS (r = 0.19; p < 0.05). A weak correlation was found for SDNN and left ventricular ejection fraction (r = 0.29; p < 0.05). There was no significant correlation between BRS and left ventricular ejection fraction (r = 0.14). In summary, there was only a weak correlation between the HRV, BRS, and left ventricular ejection fraction in patients with IDC suggesting that these 3 variables may be independent predictors of sudden death in IDC. The relative prognostic value of these variables and other potential risk predictors including the presence of arrhythmias on Holter, microvolt T wave alternans, QTc dispersion, and signal-averaged ECG is currently under investigation in a large prospective observational study (Marburg Cardiomyopathy Study (MACAS)) during 5-year follow-up at our institution.

Background: In patients with coronary artery disease, coronary angiography is performed for assessment of epicardial coronary artery stenoses. In addition, myocardial scintigraphy is commonly used to evaluate regional myocardial perfusion. These two-dimensional (2D) imaging modalities are typically reviewed through a subjective, visual observation by a physician. Even though on the analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial distribution territories of the coronary tree correspond only in 50-60% of patients. On the other hand, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. To achieve an objective assignment of each vessel segment of the coronary artery tree to the corresponding myocardial regions, we have developed a 3D 'fusion image' technique and applied it to patients with coronary artery disease. The morphological data (coronary angiography) and perfusion data (myocardial scintigraphy) are displayed in a 3D format, and these two 3D data sets are merged into one 3D image., Results: Seventy-eight patients with coronary artery disease were studied with this new 3D fusion technique. Of 162 significant coronary lesions, 120 (74%) showed good coincidence with regional myocardial perfusion abnormality on 3D fusion image. No regional myocardial perfusion abnormality was found in 44 (26%) lesions. Furthermore, the 3D fusion image revealed 24 ischemic myocardial regions that could not be related to angiographically significant coronary artery lesions., Conclusion: The results of this study demonstrate that our newly developed 3D fusion technique is useful for an accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions, and suggest that it may be helpful to improve the interpretative and decision-making process in the treatment of patients with coronary artery disease.

If cardiac MRI have been used for a long time to study cardiac morphology only, more recent developments allow the assessment of flow, perfusion and contractile function. Breath-hold segmented and MR tagging sequences offer new capabilities to explore regional functional consequences, of particular interest to characterize post-ischemic injury after myocardial infarction, representing an alternative technique to echocardiography or nuclear medicine. Combined with pharmacologic stress test, MR cardiac imaging offer a more precise characterization of myocardial perfusion and contractile function. If MR coronary angiography requires further developments, cardiac MRI have the potential to represent in the future the only imaging modality allowing combined assessment of coronary vessels, myocardial perfusion and contractile function.