Normal MPS Research Articles

Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events.

Background Both myocardial perfusion single-photon emission computed tomography (MPS) and exercise ECG (Ex-ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex-ECG improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of chronic coronary syndrome, but Ex-ECG could still be of incremental prognostic importance. Methods and Results This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex-ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS-/Ex-ECG+, n=126 and MPS+/Ex-ECG-, n=76). During follow-up, 95 events occurred. Annualized event rates significantly increased across groups (MPS-/Ex-ECG- =1.3%, MPS-/Ex-ECG+ =3.0%, MPS+/Ex-ECG- =5.1% and MPS+/Ex-ECG+ =8.0%). In multivariable analyses MPS was the strongest predictor regardless of Ex-ECG findings (MPS+/Ex-ECG-, hazard ratio [HR], 3.0, P=0.001 or MPS+/Ex-ECG+, HR,4.0, P<0.001). However, an abnormal Ex-ECG almost doubled the risk in subjects with normal MPS (MPS-/Ex-ECG+, HR, 1.9, P=0.04). Conclusions In patients with chronic coronary syndrome, combining the results from MPS and Ex-ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex-ECG to MPS, especially in patients with normal MPS.

Comparison of deep learning-based denoising methods in cardiac SPECT

BackgroundMyocardial perfusion SPECT (MPS) images often suffer from artefacts caused by low-count statistics. Poor-quality images can lead to misinterpretations of perfusion defects. Deep learning (DL)-based methods have been proposed to overcome the noise artefacts. The aim of this study was to investigate the differences among several DL denoising models.MethodsConvolution neural network (CNN), residual neural network (RES), UNET and conditional generative adversarial neural network (cGAN) were generated and trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with full, half, three-eighths and quarter acquisition time. All DL methods were compared against each other and also against images without DL-based denoising. Comparisons were made using half and quarter time acquisition data. The methods were evaluated in terms of noise level (coefficient of variation of counts, CoV), structural similarity index measure (SSIM) in the myocardium of normal patients and receiver operating characteristic (ROC) analysis of realistic artificial perfusion defects inserted into normal MPS scans. Total perfusion deficit scores were used as observer rating for the presence of a perfusion defect.ResultsAll the DL denoising methods tested provided statistically significantly lower noise level than OSEM without DL-based denoising with the same acquisition time. CoV of the myocardium counts with the different DL noising methods was on average 7% (CNN), 8% (RES), 7% (UNET) and 14% (cGAN) lower than with OSEM. All DL methods also outperformed full time OSEM without DL-based denoising in terms of noise level with both half and quarter acquisition time, but this difference was not statistically significant. cGAN had the lowest CoV of the DL methods at all noise levels. Image quality and polar map uniformity of DL-denoised images were also better than reduced acquisition time OSEM’s. SSIM of the reduced acquisition time OSEM was overall higher than with the DL methods. The defect detection performance of full time OSEM measured as area under the ROC curve (AUC) was on average 0.97. Half time OSEM, CNN, RES and UNET provided equal or nearly equal AUC. However, with quarter time data CNN, RES and UNET had an average AUC of 0.93, which was lower than full time OSEM’s AUC, but equal to quarter acquisition time OSEM. cGAN did not achieve the defect detection performance of the other DL methods. Its average AUC with half time data was 0.94 and 0.91 with quarter time data.ConclusionsDL-based denoising effectively improved noise level with slightly lower perfusion defect detection performance than full time reconstruction. cGAN achieved the lowest noise level, but at the same time the poorest defect detection performance among the studied DL methods.

Prognostic value of myocardial perfusion imaging in patients with chronic kidney disease: A systematic review and meta-analysis

BackgroundWe performed a systematic review and meta-analysis to investigate the prognostic value of stress myocardial perfusion single-photon emission computed tomography (MPS) in predicting adverse cardiovascular events in patients with chronic kidney disease (CKD). MethodsStudies published from inception until July 2020 were identified by PubMed and Embase databases search. Studies were included if they evaluated CKD patients referred for stress MPS, providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. For studies providing only non-adjusted HR, the univariable risk estimate was included in the analysis. Pooled HR and 95% confidence interval (CI) were estimated using a random effects model to compare patients with abnormal and normal MPS. Whenever possible, incidence rate ratio (IRR) was also calculated and pooled. ResultsSixteen eligible studies were identified including 7834 patients with a follow-up range from 1 to 4.4 years. Eleven articles included patients with end-stage renal disease (IV-V CKD stage), 3 articles with III-V CKD stage and 2 articles with I-V CKD stage. The pooled HR for the occurrence of adverse events was 2.02 (95% CI 1.68-2.42) and heterogeneity was 34%. Among the included studies, 5 reported the HR for the occurrence of hard events, with a pooled HR of 2.36 (95% CI 1.77-3.13). A total of 8 studies reported data useful to calculate the IRR in patients with normal and abnormal perfusion. The pooled IRR was 2.37 (95% CI 1.63-3.47) and heterogeneity was 60%. At meta-regression analysis, we found an association between HR for adverse events and age, hypertension and smoking, while no significant association was found between HR for hard events and demographic and clinical variables. ConclusionsIn patients with CKD an abnormal myocardial perfusion at stress MPS is associated with adverse cardiovascular events.

Relationship Among Coronary Artery Calcium Score, Myocardial Perfusion SPECT and Risk Stratification of Coronary Artery Disease.

Since Agatston et al. first reported quantification of the coronary artery calcification score (CACS) in 1990, discussion of its clinical significance and use in diagnostic management has continued. Recent papers have reported the relationship between CACS and myocardial perfusion single photon emission computed tomography (SPECT: MPS) and its combined diagnostic value. When interpreting CACS results, it should be noted that the frequency of significant ischemia detected by MPS, likelihood of coronary artery disease (CAD), and event rate gradually increased from mild to moderate CACS (1-400). At present, high CACS is considered to be moderately consistent with abnormal MPS, and abnormal CACS in normal MPS may contribute to CAD risk stratification. However, it should be noted that CACS=0 does not completely exclude CAD, which is particularly important when using CACS as a gatekeeper for MPS. Both stand-alone computed tomography (CT) scanner and hybrid SPECT-CT scanner are available for combined risk stratification of CACS and MPS in addition to improvement of image quality with attenuation correction.

Pretest models for predicting abnormal stress single-photon emission computed tomography myocardial perfusion imaging

BackgroundThe frequency of abnormal stress SPECT myocardial perfusion imaging (MPS) decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. These findings strengthen the need to develop more effective strategies for appropriately referring patients with suspected coronary artery disease (CAD) to cardiac imaging. The aim of this study was to develop pretest assessment models for predicting abnormal stress MPS. MethodsWe included 5,601 consecutive patients with suspected CAD, who underwent stress MPS at our academic center. Two different models were considered: a basic model including age, gender, and anginal symptoms; and a clinical model including also diabetes, hypertension, hypercholesterolemia, smoking, and family history of CAD. ResultsIn patients with abnormal MPS, the basic model classified more than 75% of patients as intermediate risk, whereas only 23% were incorrectly classified as low risk. In patients with normal MPS, 45% were correctly classified as low risk and none as high risk. Basic and clinical models had a limited discriminating capacity (area under the receiver operating characteristic curve 0.644 for basic model and 0.647 for clinical model) between individuals with and without abnormal stress MPS. The decision curve analysis demonstrates a high net benefit across a range of threshold probabilities from ~ 15% to ~30% for both models. ConclusionsA pretest risk stratification based on traditional cardiovascular risk factors has a limited value for predicting an abnormal stress MPS in patients with suspected CAD. However, selecting a proper threshold probability enhances the appropriateness of referral to stress MPS.

Long-term prognostic value of low-dose normal stress-only myocardial perfusion imaging by wide beam reconstruction: A competing risk analysis

BackgroundA normal stress myocardial perfusion single-photon emission computed tomography (MPS) is associated with a good clinical outcome. New iterative algorithms, such as wide beam reconstruction (WBR), which improve image interpretation with half-dose or half-time acquisition, have been proposed for cardiac MPS. The aim of this study was to assess the long-term predictive value of a low-dose normal stress-only MPS with WBR using conventional Anger camera in patients with known or suspected coronary artery disease (CAD). Methods and ResultsA total of 2106 patients with known or suspected CAD and normal perfusion at half-dose stress-only MPS protocol were followed for a mean of 6.6 ± 2.7 years. MPS data were reconstructed with WBR iterative algorithm. End-point events were cardiac death or nonfatal myocardial infarction. Noncardiac death was considered the competing event. During follow-up, 149 cardiac events occurred with an annualized event rate of 1.2%. Independent predictors of cardiac events at Cox analysis were age, male gender, diabetes mellitus, previous myocardial infarction and the need for pharmacologic stress testing. At Fine-Gray analysis the cumulative incidence of cardiac events progressively increases with age and in the presence of diabetes for any combination of gender and stress type. Survival tree analysis confirmed that long-term prognosis considerably varies according of risk factors profile. ConclusionsLow-dose normal stress-only WBR MPS has a reliable long-term prognostic value in patients with suspected or known CAD. This finding supports the introduction of such a method into clinical practice with a consistent dose optimization in the interest of patients and exposed staff.

Warranty period of normal stress myocardial perfusion imaging in hypertensive patients: A parametric survival analysis

BackgroundWe evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients. Methods and ResultsA total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months. ConclusionsIn hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

The Relationship Between Absence Coronary Artery Calcification and Myocardial Perfusion Single Photon Emission Computed Tomography

BackgroundCoronary artery calcification score (CACS) is well validated prognostic tool in coronary artery disease (CAD). The data on the prevalence of myocardial ischemia on myocardial perfusion single photon emission computed tomography (MPS) in symptomatic patients with zero CACS and low to intermediate risk probability is lacking and controversial. The aim of our study was to evaluate the capability of zero CACS to exclude myocardial ischemia on MPS.MethodsA total of 157 patients ((mean age 53 ± 10 years), 88 (56%) female patients, 69 (44%) male patients) who were suspected to have CAD and having low to intermediate pretest likelihood for CAD underwent CACS on dedicated computed tomography (CT) scanners. CACS was reported as zero in all patients, subsequently all patients underwent MPS. Patients with abnormal MPS underwent additional imaging with coronary computed tomography angiography (CCTA).ResultsAll patients had zero CACS, of which 122 (78%) had normal MPS, and 35 (22%) had abnormal MPS. Abnormal MPS included fixed defect in 22 (13%), equivocal in 10 (6%), and reversible defect in four (3%) patients. All patients with abnormal MPS had further imaging with CTCA. CTCA was normal in 30 (85%) patients, one patient had coronary artery stenosis more than 50%, one patient had coronary artery stenosis less than 50%, one patient had anomalous origin coronary artery, and two patients had myocardial bridging. Patients with abnormal MPS and normal coronary artery had dilated cardiomyopathy in 14 (40%), asymmetrical septal hypotrophy in one (3%), and mitral valve disease in three (9%).ConclusionsZero CACS in stable patients with low or intermediate risk indicated very low likelihood of obstructive CAD, less than 1%. Patients with zero CACS and normal MPS most likely will not benefit from further testing; however, patients with abnormal MPS will need further imaging with CCTA. CCTA is helpful in this group of patients for evaluation of coronary artery and cardiac morphology.

Quality of life as predictor for the development of cardiac ischemia in high-risk asymptomatic diabetic patients

BackgroundIschemia induced by psychological stress and depression is a common phenomenon in stable coronary artery disease (CAD). We evaluated the quality of life (QoL) of diabetic patients screened for CAD and assessed the prognostic value of mental and physical QoL scores to predict the development of new cardiac ischemia. MethodsProspective multicentre outcome study. The study comprised 400 asymptomatic diabetic patients without history or symptoms of CAD. They underwent myocardial perfusion single-photon emission computed tomography (MPS) and assessment of QoL by two questionnaires: Hospital Depression and Anxiety Scale (HADS-D and HADS-A) and Medical Outcomes Study Short Form 36 (SF-36) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management. ResultsOnly mental QoL scores but not physical QoL scores or traditional cardiovascular risk factors were predictive of new ischemia (n = 11/306) during follow-up. The prognostic value for new ischemia as quantified by the area under the receiver operating characteristics curve (AUC) amounted to 0.784 (95% confidence interval (CI) 0.654-0.914, P = 0.002) for HADS-D and to 0.737 (95% CI 0.580-0.893, P = 0.011) for HADS-A. This finding was confirmed by SF-36 mental sum score (AUC 0.688, 95% CI 0.539-0.836, P = 0.036), but not SF-36 physical sum score. QoL scores did not change after 2 years in patients with ischemia at baseline. ConclusionsQoL scores assessing mental health, particularly depression and anxiety, predicted the development of new cardiac ischemia in asymptomatic diabetic patients. The study is limited by a small number of events (new ischemia) and so the results should be considered hypothesis generating rather than conclusive.

Breast Arterial Calcifications on Mammography Do Not Predict Myocardial Ischemia on Myocardial Perfusion Single-Photon Emission Computed Tomography.

BackgroundThe aim of this study was to determine if breast arterial calcification (BAC) on mammography predicts myocardial ischemia (MI) on stress myocardial perfusion single-photon emission computed tomography (MPS). BAC is a type of medial artery calcification that can be seen incidentally on mammography, but the relationship between coronary artery calcification and MI on MPS is yet unknown.MethodsA total of 435 consecutive women underwent mammography and stress MPS within 1 year of each other. BAC was quantitatively evaluated (0 - 13). Patients with known coronary artery diseases (CADs) such as coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), MI, positive coronary angiogram or positive MPS were excluded from the study. Risk factors for CAD were obtained from a chart review.ResultsThe mean age was 58 ± 8 years. BAC was found in 258 (59%) of the study population. BAC-positive patients were significantly older than BAC-negative patients (P < 0.0001), there were strong associations between BAC and hypertension (P = 0.0309), chronic kidney disease (CKD) (P = 0.0001), and diabetes (P = 0.0309), but there were significant associations between BACV and hyperlipidemia, family history of CAD, and smoking (P = 0.6856, P = 0.9642, and P = 0.087, respectively). The mean score of BAC was 5 ± 5 in patients with normal MPS and was 6 ± 6 in patients with abnormal MPS. There were no associations between total BAC and MPS results (P = 0.2095), and between BAC categories and MPS result (P = 0.3069).ConclusionsBased on our study, the presence and severity of BAC on screening or diagnostic mammography do not predict MI on stress MPS, and further cardiac workup based on the presence of BAC is not warranted. BAC is very common in mammography up to 59% and associated with age, diabetes, CKD, and hypertension. In contrast, the prevalence of MI is only 13% in women with BAC and associated with age, diabetes, CKD, hyperlipidemia, and impaired left ventricular function.

Screening asymptomatic patients with type 2 diabetes is recommended: Pro

Cardiovascular morbidity is common in type 2 diabetes mellitus (DM) and several epidemiological studies reported that DM is associated with a marked increase in the risk of coronary artery disease (CAD). In 1999, the Finnish diabetologist, Yki-Jarvinen, provocatively stated: ‘‘diabetes is a cardiovascular disease which you diagnose by measuring the blood glucose.’’ In the same year, also the American Heart Association stated that it might be appropriate to say ‘‘diabetes is a cardiovascular disease.’’ At this time, DM is commonly considered as a CAD risk equivalent in many position papers and guidelines. However, screening asymptomatic DM subjects for detection of CAD and subsequent management remains controversial. It is well known that patients with DM and inducible myocardial ischemia are often asymptomatic and when CAD becomes clinically manifest it is frequently in an advance stage. Also episodes of transitory myocardial ischemia may be ‘‘silent’’ and abnormal asymptomatic ST changes may be recorded during ambulatory ECG monitoring. The exact prevalence of silent ischemia in DM remains unidentified. A review of studies assessing the presence of stress-induced ischemia by myocardial perfusion single-photon emission computed tomography (MPS) in asymptomatic diabetic patients with unrecognized CAD reported a prevalence ranging from 4% to 62%, largely due to the different patients characteristics. The annual event rate ranged from 2.4% to 5.8% in subjects with abnormal MPS and from 0.4% to 2.1% in those with normal MPS. At this time, largely based on the results of the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, the American Diabetes Association does not recommend screening for CAD in asymptomatic patients because it does not improve outcomes as long as cardiovascular risk factors are treated (level of evidence A). However, according to the European Society of Cardiology guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the European Association for the Study of Diabetes, this issue is still under debate and the characteristics of the patients who should be screened for CAD need to be better defined. In addition, the detection of occult CAD might allow the initiation of appropriate therapy at a time point when the disease process is more easily modifiable. Thus, testing of asymptomatic diabetic patients for risk stratification purposes is a paramount objective of cardiovascular imaging and this strategy is expected to lead to declines in cardiac morbidity and mortality. In this context, certain important questions are still to be addressed, such as the potential of coronary revascularization to reduce cardiac events in asymptomatic patients; the yield of non-invasive testing in identifying, reliably, a considerable proportion of those patients likely to benefit from this type of intervention in a cost-effective manner; and the questions of who, when and how to test. The Impact of in Ducible Ischemia by Stress MPS (IDIS) trial was designed to evaluate if in patients with DM the use of an aggregate score incorporating and weighting multiple risk factors could be superior to an approach based on the number of risk factors to define the patient’s risk. This multicentre study enrolled 822 consecutive patients with DM, and risk estimates for a CAD event were categorized as 0% to\3%, 3% to\5%, and C5% per year using Cox proportional hazards models. Model 1 used traditional CAD risk factors and ECG stress test data and model 2 used these variables plus MPS imaging data. CAD death, myocardial infarction, and unstable angina requiring coronary revascularization were the outcome measures. During follow-up (58 ± 11 months), 148 events occurred. Model 2 improved risk prediction compared to model 1 Reprint requests: Alberto Cuocolo, MD, Department of Advanced Biomedical Sciences, University Federico II, Via Pansini 5, 80131, Naples, Italy; cuocolo@unina.it J Nucl Cardiol 2015;22:1225–8. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.

Prognostic value of normal stress myocardial perfusion imaging in diabetic patients: A meta-analysis

BackgroundThe prognostic value of normal stress myocardial perfusion single-photon emission computed tomography (MPS) in patients with diabetes has only been evaluated in single-center studies of relatively limited sample size. We performed a meta-analysis of published studies, including diabetic patients with known or suspected coronary artery disease (CAD), to assess the predictive value for adverse cardiac ischemic events of normal stress MPS. Methods and ResultsStudies published between January 1990 and December 2013 were identified by database search. We included studies using stress MPS to evaluate diabetic patients with known or suspected CAD and providing data on clinical outcomes of non-fatal myocardial infarction or cardiac death with a follow-up time ≥12 months. A total of 14 studies were finally included, recruiting 13,493 patients. The negative predictive value (NPV) for non-fatal myocardial infarction and cardiac death of normal MPS was 94.92% (95% confidence interval 93.67-96.05), during a weighted mean follow-up of 36.24 months, resulting in estimated event rate after a negative test equal to 5.08% (95% confidence interval 3.95-6.33). The corresponding annualized event rate after a negative test was 1.60% (95% confidence interval 1.21-2.04). ConclusionsStress MPS has a high NPV for adverse cardiac events in diabetic patients with known or suspected CAD leading to define a “relatively low-risk” patients category.

Progression to Overt or Silent CAD in Asymptomatic Patients With Diabetes Mellitus at High Coronary Risk: Main Findings of the Prospective Multicenter BARDOT Trial With a Pilot Randomized Treatment Substudy

ObjectivesThe purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk. BackgroundDespite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking. MethodsProspective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management. ResultsAn abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001). ConclusionsHigh-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a 7-fold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patients’ outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632).

Prognostic value of myocardium perfusion imaging with a new reconstruction algorithm

BackgroundIt has been demonstrated that a new reconstruction algorithm for myocardium perfusion imaging (MPI) allows faster acquisition with similar accuracy. The prognostic value of MPI performed with this software and short acquisition time is unknown. MethodsTo determine the prognostic value we followed 3184 consecutive MPI patients between March 2008 and March 2010. A 2-day protocol with low dose 99mTc-MIBI (10-12 mCi) and a 6-minute acquisition was used. Exercise stress was used in 62.6 % of the studies. Scans were reconstructed using the software “Evolution for cardiac”. Perfusion defects were quantified by summed stress score (SSS) and categorized in four groups: SSS0 = 0; SSS1 = 1-3; SSS2 = 4-8; and SSS3 ≥ 9. Patients were phone contacted every 6 months for follow up and hard events were defined as death or myocardial infarction (MI) and total events as hard events plus late revascularization. ResultsThe mean radiation dose was <7 mSv/patient. Mean F/U was 33 ± 20 months; 140 of the patients were lost to follow up and 86 were censored due early revascularization (<60 days after MPS). There were 140 hard events: 89 deaths and 51 MI. Mean age was 61.5 ± 12.3 years and 57.7 % were male. Hard event rate was 0.8 %/year in patients with normal MPS and 3.7 %/year in those with abnormal MPS. Patients with larger defects had nine times more hard events than patients with SSS = 0 (14.2 % vs 1.6 %). Revascularization was more frequent in patients with abnormal MPS than normal MPS (21.7 % vs 3.9 %; P < 0.001). Cox proportional hazard analysis showed that SSS was an independent predictor of hard events and revascularization. ConclusionsThe use of reduced-dose, fast myocardial perfusion SPECT and the new processing algorithm lowers acquisition time and radiation exposure compared to conventional SPECT without compromising the well-established prognostic value of MPI.

Warranty period of normal stress myocardial perfusion imaging in diabetic patients: A propensity score analysis

BackgroundWe evaluated the relationship between diabetes and temporal characteristics of cardiac risk at long-term follow-up in a propensity score-matched cohort of diabetic and non-diabetic patients with normal stress myocardial perfusion single-photon emission computed tomography (MPS). Methods and ResultsWe studied 828 consecutive patients with suspected or known coronary artery disease and normal perfusion at stress MPS. To account for differences in baseline characteristics between diabetics and non-diabetics, we created a propensity score-matched cohort considering clinical variables and stress type. After matching, clinical characteristics were comparable in 260 diabetic and 260 non-diabetic patients. All patients were followed for at least 1 year (median 53 months). End-point events were cardiac death or nonfatal myocardial infarction. At Cox analysis, diabetes (hazard ratio 3.9, P < .01) and post-stress left ventricular ejection fraction (LVEF) ≤45% (hazard ratio 4.1, P < .01) were independent predictors of events. At parametric analysis, non-diabetic patients with post-stress LVEF >45% remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration was observed in patients with diabetes and post-stress LVEF ≤45%. ConclusionsAfter a normal stress MPS, diabetic patients are at higher risk for cardiac events than non-diabetic subjects also after balancing clinical characteristics and stress type by propensity score analysis. The warranty period of a normal stress MPS varies according to diabetic status and post-stress LVEF.

Magnetic resonance imaging and spectroscopy to evaluate muscle involvement in Pompe disease

in filter paper, initially for the detection of heparan sulfamidase (MPS IIIA) and beta-galactosidase (GM1-gangliosidosis, MPS IVB, galactosialidosis) deficiencies. We prepared filter paper samples with dried-leukocytes or dried-fibroblast (DLFP, DFFP) from healthy individuals and from patients with confirmed MPS IIIA or GM1 gangliosidosis by direct transfer of cell homogenates to filter paper discs. Heparan sulfaminidase and beta-galactosidase were tested by incubating samples with specific buffers and substrates. For heparan sulfamidase, a clear discrimination was found between normal controls and MPS IIIA patients both in DLFP and DFFP samples. For beta-galactosidase, distinction between normal controls and GM1-gangliosisdosis patients was evidenced only in DLFP samples so far. Although the method still needs further development, we conclude that assays for these two enzymes could be performed in dried-cell homogenates, and could be an useful tool for LSD identification, especially in areas where liquid blood samples usually need to travel several days to reach the reference laboratory.

Genotyping analysis available for patients after hematopoietic cell transplantation for multiple types of lysosomal diseases

in filter paper, initially for the detection of heparan sulfamidase (MPS IIIA) and beta-galactosidase (GM1-gangliosidosis, MPS IVB, galactosialidosis) deficiencies. We prepared filter paper samples with dried-leukocytes or dried-fibroblast (DLFP, DFFP) from healthy individuals and from patients with confirmed MPS IIIA or GM1 gangliosidosis by direct transfer of cell homogenates to filter paper discs. Heparan sulfaminidase and beta-galactosidase were tested by incubating samples with specific buffers and substrates. For heparan sulfamidase, a clear discrimination was found between normal controls and MPS IIIA patients both in DLFP and DFFP samples. For beta-galactosidase, distinction between normal controls and GM1-gangliosisdosis patients was evidenced only in DLFP samples so far. Although the method still needs further development, we conclude that assays for these two enzymes could be performed in dried-cell homogenates, and could be an useful tool for LSD identification, especially in areas where liquid blood samples usually need to travel several days to reach the reference laboratory.

The prognostic significance of typical perfusion defects on vasodilator stress myocardial perfusion SPECT in patients with left bundle branch block or right ventricular apical pacing

Left bundle branch block (LBBB) and ventricular pacing may induce typical artefacts that appear as perfusion defects in myocardial perfusion single photon emission computed tomography (MPS). We assessed the prognosis of patients with LBBB or right ventricular apical (RVA) pacing who had chest pain and an MPS with only abnormal activation-related defects (AARD). All patients with LBBB or ventricular pacing referred for vasodilator stress MPS between April 2002 and January 2006 were analyzed. AARD were defined as small, nontransmural, fixed defects and small reversible defects in well-defined regions always accompanied with concomitant wall motion abnormalities. Ninety-seven patients were included, with a mean follow-up period of 3+/-1.3 years. MPS showed AARD in 57 and it was completely normal in 40 patients. No significant difference in cumulative cardiac event-free follow-up was observed between patients with AARD (93%) and normal MPS (85%). The average annual cardiac event rate was not significantly different between the groups (1.7 and 4.3% per year, respectively). No difference was found between patients with LBBB and RVA pacing. Patients with chest pain and LBBB or RVA pacing who show AARD on MPS have a comparable prognosis as patients with abnormal activation and a normal MPS. This justifies MPS for risk stratification of patients with chest pain and LBBB or RVA pacing.

Predictive Value of Myocardial Perfusion Single-Photon Emission Computed Tomography and the Impact of Renal Function on Cardiac Death

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

Circulating Microparticles in Normal Pregnancy and Pre-Eclampsia

Cellular particles may be larger shed microparticles (≥100 nm, MPs) that are the products of cell activation or necrosis. There are also smaller endocytic nanoparticles (<100 nm), called exosomes, which are internal vesicles of late endosomes or multivesicular bodies and are released into the extracellular milieu upon fusion of the multivesicular body with the cell surface. Both MPs and exosomes can be detected in the circulations of non-pregnant and pregnant women. In the former MPs are increased in conditions associated with systemic inflammation such as sepsis or metabolic syndrome. During normal pregnancy MPs are increased and they increase further with pre-eclampsia. They include not only MPs derived from platelets, endothelium and various leukocytes but also syncytiotrophoblast derived MPs (often called STBMs). STBMs interact with both immune and endothelial cells and may contribute to the systemic inflammation of both normal and pre-eclamptic pregnancies. However inhibitory activity has also been ascribed to trophoblast derived exosomes. In vitro, they down-regulate T cell activity, a T cell change that has been repeatedly observed, ex vivo, during normal pregnancy.