Search

First introduced in 1976, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18F-FDG uptake increased due to hypoxia. 18F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18F-FDG uptake and hypoxia, the possible mechanism of 18F-FDG uptake caused by hypoxia, and the associated clinical implications.

Conventional single photon emission computed tomography (SPECT) relies on mechanical collimation whose resolution and sensitivity are interdependent, the best performance a SPECT system can attain is only a compromise of these two equally desired properties. To simultaneously achieve high resolution and sensitivity, we propose to use sensitive detectors constructed in a m ulti-l a yer in t e r spaced mosa ic d e tector s (MATRICES) architecture to accomplish part of the collimation needed. We name this new approach self-collimation. We evaluate three self-collimating SPECT systems and report their imaging performance: 1) A simulated human brain SPECT achieves 3.88% sensitivity, it clearly resolves 0.5-mm and 1.0-mm hot-rod patterns at noise-free and realistic count-levels, respectively; 2) a simulated mouse SPECT achieves 1.25% sensitivity, it clearly resolves 50- $\mu \text{m}$ and 100- $\mu \text{m}$ hot-rod patterns at noise-free and realistic count-levels, respectively; 3) a SPECT prototype achieves 0.14% sensitivity and clearly separates 0.3-mm-diameter point sources of which the center-to-center neighbor distance is also 0.3 mm. Simulated contrast phantom studies show excellent resolution and signal-to-noise performance. The unprecedented system performance demonstrated by these 3 SPECT scanners is a clear manifestation of the superiority of the self-collimating approach over conventional mechanical collimation. It represents a potential paradigm shift in SPECT technology development.

BACKGROUND: Establishing appropriate reference value limits of left ventricular (LV) functional parameters is fundamental for the assessment of cardiac function. At present, there are no reports aimed at establishing reference limits using gated myocardial perfusion imaging (MPI) in mainland China. METHODS: A total of 175 consecutive patients who were defined as low-risk coronary artery disease patients underwent stress Technetium-99m sestamibi ((99m)Tc-MIBI)-gated myocardial perfusion single-photon emission computed tomography (SPECT) imaging. The LV ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) were obtained by 3 quantitative algorithms: quantitative-gated SPECT, emory cardiac toolbox, and 4-dimensional model SPECT, respectively. The threshold values were obtained using Gaussian distribution or percentiles. The influence of gender, age, and weight on cardiac functional parameters was analyzed by multiple regressions for linear models. RESULTS: For males, the lower reference limits of EF were 52%, 63%, and 58%, respectively; and the upper limits of EDV/ESV were 106/45, 152/55, and 135/55 mL, respectively. For females, the lower reference limits of EF were 58%, 66%, and 65%, respectively; and the upper limits of EDV/ESV were 73/27, 105/31, and 88/29 mL, respectively. Compared to females, males had greater cardiac volume values and lower mean EF values. Bland-Altman plots revealed that the cardiac function parameters calculated by the three quantitative algorithms were in high agreement. CONCLUSIONS: In this study, the reference limits of cardiac parameters calculated by the 3 methods based on single-center data in China were preliminarily established. The threshold values determined by three quantitative algorithms were not interchangeable but were highly correlated.

Background: It has been confirmed that the α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for identifying vulnerable atherosclerotic plaques. Previously, we successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR, which are mainly used in the diagnosis of Alzheimer's disease. Based on the characteristics of α7nAChR in blood vessels, we have firstly screened for a suitable novel 18F-labeled PET molecular probe ([18F]YLF-DW), with high selectivity for α7nAChR over α4β2nAChR and a good effect for the imaging of atherosclerotic animal models, to effectively identify vulnerable atherosclerotic plaques at an early stage. Meanwhile, we compared it with the “gold standard” pathological examination of atherosclerosis, to verify the reliability of [18F]YLF-DW in early diagnosis of atherosclerosis.Methods: The vulnerable atherosclerotic plaques model of ApoE-/-mice were successfully established. Then based on the methods of 3D-QSAR and molecular docking, we designed oxazolo[4,5-b] pyridines and fluorenone compounds, which are targeted at α7nAChR. Through further screening, a novel alpha7 nicotinic acetylcholine receptor radioligand ([18F]YLF-DW) was synthesized and automatically 18F-labeled using a Stynthra RNplus module. Subsequently, we employed [18F]YLF-DW for the targeting of α7nAChR in atherosclerotic plaques and control group, using a micro-PET/CT respectively. After imaging, the mice were sacrificed by air embolism and the carotid arteries taken out for making circular sections. The paraffin embedded specimens were sectioned with 5 μm thickness and stained with oil red. After staining, immunohistochemistry experiment was carried out to verify the effect of micro-PET/CT imaging.Results: The micro-PET/CT imaging successfully identified the vulnerable atherosclerotic plaques in the carotid arteries of ApoE-/-mice; whereas, no signal was observed in normal control mice. In addition, compared with the traditional imaging agent [18F]FDG, [18F]YLF-DW had a significant effect on the early plaques imaging of carotid atherosclerosis. The results of oil red staining and immunohistochemistry also showed early formations of carotid plaques in ApoE-/-mice and provided pathological bases for the evaluation of imaging effect.Conclusion: We innovated to apply the novel molecular probe ([18F]YLF-DW) to the identification of vulnerable atherosclerotic plaques in carotid arteries, to detect atherosclerosis early inflammatory response and provide powerful input for the early diagnosis of atherosclerotic lesions, which may play an early warning role in cardiovascular acute events.

Background: It has been confirmed that the α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for identifying vulnerable atherosclerotic plaques. Previously, we successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR, which are mainly used in the diagnosis of Alzheimer's disease. Based on the characteristics of α7nAChR in blood vessels, we have firstly screened for a suitable novel 18F-labeled PET molecular probe ([18F]YLF-DW), with high selectivity for α7nAChR over α4β2nAChR and a good effect for the imaging of atherosclerotic animal models, to effectively identify vulnerable atherosclerotic plaques at an early stage. Meanwhile, we compared it with the “gold standard” pathological examination of atherosclerosis, to verify the reliability of [18F]YLF-DW in early diagnosis of atherosclerosis. Methods: The vulnerable atherosclerotic plaques model of ApoE-/-mice were successfully established. Then based on the methods of 3D-QSAR and molecular docking, we designed oxazolo[4,5-b] pyridines and fluorenone compounds, which are targeted at α7nAChR. Through further screening, a novel alpha7 nicotinic acetylcholine receptor radioligand ([18F]YLF-DW) was synthesized and automatically 18F-labeled using a Stynthra RNplus module. Subsequently, we employed [18F]YLF-DW for the targeting of α7nAChR in atherosclerotic plaques and control group, using a micro-PET/CT respectively. After imaging, the mice were sacrificed by air embolism and the carotid arteries taken out for making circular sections. The paraffin embedded specimens were sectioned with 5 μm thickness and stained with oil red. After staining, immunohistochemistry experiment was carried out to verify the effect of micro-PET/CT imaging. Results: The micro-PET/CT imaging successfully identified the vulnerable atherosclerotic plaques in the carotid arteries of ApoE-/-mice; whereas, no signal was observed in normal control mice. In addition, compared with the traditional imaging agent [18F]FDG, [18F]YLF-DW had a significant effect on the early plaques imaging of carotid atherosclerosis. The results of oil red staining and immunohistochemistry also showed early formations of carotid plaques in ApoE-/-mice and provided pathological bases for the evaluation of imaging effect. Conclusion: We innovated to apply the novel molecular probe ([18F]YLF-DW) to the identification of vulnerable atherosclerotic plaques in carotid arteries, to detect atherosclerosis early inflammatory response and provide powerful input for the early diagnosis of atherosclerotic lesions, which may play an early warning role in cardiovascular acute events.

Wound healing is regulated by a complex series of events and overlapping phases. A delicate balance of cytokines and mediators in tissue repair is required for optimal therapy in clinical applications. Molecular imaging technologies, with their versatility in monitoring cellular and molecular events in living organisms, offer tangible options to better guide tissue repair by regulating the balance of cytokines and mediators at injured sites. Methods: A murine cutaneous wound healing model was developed to investigate if incorporation of prostaglandin E2 (PGE2) into chitosan (CS) hydrogel (CS+PGE2 hydrogel) could enhance its therapeutic effects. Bioluminescence imaging (BLI) was used to noninvasively monitor the inflammation and angiogenesis processes at injured sites during wound healing. We also investigated the M1 and M2 paradigm of macrophage activation during wound healing. Results: CS hydrogel could prolong the release of PGE2, thereby improving its tissue repair and regeneration capabilities. Molecular imaging results showed that the prolonged release of PGE2 could ameliorate inflammation by promoting the M2 phenotypic transformation of macrophages. Also, CS+PGE2 hydrogel could augment angiogenesis at the injured sites during the early phase of tissue repair, as revealed by BLI. Furthermore, our results demonstrated that CS+PGE2 hydrogel could regulate the balance among the three overlapping phases—inflammation, regeneration (angiogenesis), and remodeling (fibrosis)—during cutaneous wound healing. Conclusion: Our findings highlight the potential of the CS+PGE2 hydrogel as a novel therapeutic strategy for promoting tissue regeneration via M2 macrophage polarization. Moreover, molecular imaging provides a platform for monitoring cellular and molecular events in real-time during tissue repair and facilitates the discovery of optimal therapeutics for injury repair by regulating the balance of cytokines and mediators at injured sites.

Transplantation of endothelial cells (ECs) holds great promise for treating various kinds of ischemic diseases. However, the major challenge in ECs-based therapy in clinical applications is to provide high quality and enough amounts of cells. In this study, we developed a simple and efficient system to direct endothelial differentiation of mouse embryonic stem cells (ESCs) using a controllable chitosan nitric oxide (NO)-releasing hydrogel (CS-NO). ESCs were plated onto the hydrogel culture system, and the expressions of differentiation markers were measured. We found that the expression of Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) increased obviously under the controlled NO releasing environment. Moreover, the Flk-1 upregulation was accompanied by the activation of the phospho-inositide-3 kinase (PI3K)/Akt signaling. We also found that in the presence of the PI3K inhibitor (LY294002), the endothelial commitment of ESCs was abolished, indicating the importance of Akt phosphorylation in the endothelial differentiation of ESCs. Interestingly, in the absence of NO, the activation of Akt phosphorylation alone by using AKT activator (SC-79) did not profoundly promote the endothelial differentiation of ESCs, suggesting an interdependent relationship between NO and the Akt phosphorylation in driving endothelial fate specification of ESCs. Taken together, we demonstrated that NO releasing in a continuous and controlled manner is a simple and efficient method for directing the endothelial differentiation of ESCs without adding growth factors. Statement of Significance Fascinating data continues to show that artificial stem cell niche not only serve as a physical supporting scaffold for stem cells proliferation, but also as a novel platform for directing stem cell differentiation. Because of the lack of proper microenvironment for generating therapeutic endothelial cells (ECs) in vitro, the source of ECs for transplantation is the major limitation in ECs-based therapy to clinical applications. The current study established a feeder cell-free, 2-dimensional culture system for promoting the differentiation processes of embryonic stem cells (ESCs) committed to the endothelial lineage via using a nitric oxide (NO) controlled releasing hydrogel (CS-NO). Notably, the NO releasing from the hydrogel could selectively up-regulate Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) in the absence of growth factors, which was of crucial importance in the endothelial differentiation of ESCs. In summary, the current study proposes a simple and efficient method for directing the endothelial differentiation of ESCs without extra growth factors.

Aims Patients with unexplainable giant T-wave inversion in the precordial leads and apical wall thickness

Myocardial perfusion imaging (MPI), using radiotracers, has been in routine clinical use for over 40 years. This modality is used for the detection of coronary artery disease (CAD), risk stratification, optimizing therapy, and follow-up of patients with CAD. Molecular cardiovascular imaging using targeted radiotracers provides a unique opportunity for imaging biochemical and metabolic processes, and cell membrane transporter and receptor functions at a cellular and molecular level in experimental animal models as well as in humans. Cardiac imaging using radiolabeled free fatty acid analogues and glucose analogues enable us to image myocardial ischemia directly as an alternative to stress-rest MPI. Direct ischemia imaging techniques can avoid and overcome some of the limitations of standard stress-rest MPI. This article describes recent studies using (18) F-fluorodeoxyglucose ((18) FDG) for myocardial ischemia imaging.

Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

Resident cardiac stem cells (CSCs) represent a responsive stem cell reservoir within the adult myocardium and have a significant function in myocardial homeostasis and injury. However, the distribution, origin, homing and possible therapeutic benefits of CSCs are still under discussion. Here we investigated whether bone marrow (BM) stem cells could contribute to repopulating the pool of CSCs in heart. The engraftment of BM cells in heart was detected at a low level after BM transplantation (BMT) and ischemia/reperfusion (I/R) could increase BM cells engraftment but not significant. We clarified that more than 50% CSCs are derived from BM and confirmed that BM-derived CSCs have similar characteristics with the host CSCs. Furthermore, we transplanted BM-derived CSCs into heart ischemia models and presented evidence for the first time that BM-derived CSCs can differentiate into cardiomyocytes in vivo. In conclusions, BM stem cells could be a potential back-up source of CSCs for restoring heart function after injury or maintaining homeostasis of CSCs.

Background— Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required. Methods and Results— One-hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient ≥50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased ≥50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment ( r =0.371; P r =0.527; P r =0.672; P P Conclusions— Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA.

Purpose To evaluate the feasibility of free-breathing three-dimensional (3D) phase sensitive inversion recovery (PSIR) Turbo FLASH late gadolinium enhancement (LGE) magnetic resonance images (MRI) on left ventricular scar in patients with coronary artery disease (CAD) compared with clinically established breathhold two-dimensional (2D) PSIR Turbo FLASH images. Materials and Methods In 58 consecutive patients with confirmed CAD, LGE MRI using the two sequences have been acquired. Image quality was graded on a four-point scale according to the image appearance. Qualitative evaluation including the distribution area and the transmural extent of the scar based on the American Heart Association's (AHA's) 17-segment model was performed in both of 2D and 3D images. The scar volumes were compared quantitatively between 2D and 3D images. Results A total of 51 individuals were used for final statistical analysis. No differences were noted in image quality (P = 0.80), scar distribution area (P = 0.17), and scar transmural extent (P = 0.20) between 3D and 2D images. There was strong correlation in scar volume between the 3D and 2D results (r = 0.940; P < 0.001; Y = 0.298 + 1.251X, R2 = 0.876). But the scar volume derived from 3D images was significantly larger than that derived from 2D images (2D versus 3D, 20.08 ± 9.41 cm3 versus 25.41 ± 12.57 cm3, t = −7.60; P < 0.001). The trend toward a larger scar volume identified by 3D method was indicated through Bland-Altman analysis. Conclusion Free-breathing 3D PSIR Turbo FLASH imaging is another feasible method to identify left ventricular myocardial scar in patients with CAD and detects more scar volume compared with breathhold 2D PSIR Turbo FLASH imaging. J. Magn. Reson. Imaging 2013;38:72–79. © 2012 Wiley Periodicals, Inc.

This study measured glucose uptake in the right ventricle (RV) of patients with pulmonary hypertension and investigated the relationship to hemodynamics and survival. Myocardial 18F-fluorodeoxy-glucose (FDG) uptake was measured using single-photon positron emission tomography (SPECT) in 24 patients with idiopathic pulmonary arterial hypertension (IPAH) and 43 patients with congenital heart disease (CHD). In both IPAH and CHD-PAH, RV FDG uptake (RV/LV ratio) was associated with pulmonary vascular resistance (PVR). A second SPECT scan was performed in nine patients after 6 months treatment with sildenafil. PVR decreased from 1683±426 to 1207±383 dyn s-1 cm-5 (P < 0.05) and cardiac index improved from 2.2±0.2 to 2.8±0.5 L/min/m2 (P < 0.01). RV/LV FDG uptake decreased from 1.28±0.32 before treatment to 0.99±0.23 (P < 0.05). Survival in the IPAH group with a baseline RV/LV FDG uptake greater than the median value of 1.20 was significantly lower than that of the group with RV/LV FDG uptake below 1.20 (log-rank test, P < 0.05). In contrast, baseline RV/LV FDG was of little informative value in CHD. FDG uptake by the RV reflects the severity of PVR in PAH. Increased RV FDG uptake is a marker of poor prognosis in IPAH and is reduced in patients receiving effective therapy. It could prove useful in the early clinical assessment of novel therapies for PAH.

This prospective study evaluated the accuracy of electrocardiogram-gated blood-pool SPECT (GBPS) for the assessment of left ventricular (LV) and right ventricular (RV) ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) in patients with dilated cardiomyopathy (DCM), using cardiac magnetic resonance (CMR) imaging as the reference standard.Thirty-two patients (24 men and 8 women; mean age, 51 y) with a diagnosis of idiopathic DCM underwent GBPS and CMR. LV and RV parameters including EDV, ESV, and EF from GBPS were calculated using fully automated gradient software and compared with those obtained by CMR.Biventricular volumes were underestimated by GBPS, compared with CMR (P0.001). We found no statistical difference between these 2 methods in the assessment of LV EF (P = 0.23), whereas RV EF was overestimated by GBPS (P0.001 vs. CMR). Regression analysis yielded significant correlations between GBPS and CMR in the assessments of biventricular parameters (r = 0.83 for LV EDV, 0.88 for LV ESV, 0.89 for LV EF, 0.86 for RV EDV, 0.86 for RV ESV, and 0.62 for RV EF; all P0.001). Comparison of the deviations of RV indices between GBPS and CMR with the ratio of RV EDV to LV EDV showed that there was a statistically significant trend for RV volumes to be underestimated and for RV EF to be overestimated as the biventricular volumetric ratio decreased (r = 0.61 for RV EDV, 0.68 for RV ESV, and -0.55 for RV EF; all P0.001).For patients with DCM, GBPS correlated well with CMR for the assessment of biventricular parameters, but RV indices should be cautiously interpreted.

Objectives This study aimed at examining the efficacy of bone marrow mononuclear cell (BMMNC) delivery through graft vessel for patients with a previous myocardial infarction (MI) and chronic heart failure during coronary artery bypass graft (CABG). Background Little evidence exists supporting the practice of BMMNC delivery through graft vessel for patients with a previous MI and chronic heart failure during CABG. Methods From November 2006 to June 2009, a randomized, placebo-controlled trial was conducted to test the efficacy and safety of CABG for multivessel coronary artery disease combined with autologous BMMNCs in patients with congestive heart failure due to severe ischemic cardiomyopathy. Sixty-five patients were recruited, and 60 patients remained in the final trial and were randomized to a CABG + BMMNC group (n = 31) and a placebo-control group (i.e., CABG-only group, n = 29). All patients discharged received a 6-month follow-up. Changes in left ventricular ejection fraction from baseline to 6-month follow-up, as examined by magnetic resonance imaging, were of primary interest. Results The overall baseline age was 59.5 ± 9.2 years, and 6.7% were women. After a 6-month follow-up, compared with the placebo-control group, the CABG + BMMNC group had significant changes in left ventricular ejection fraction (p = 0.029), left ventricular end-systolic volume index (p = 0.017), and wall motion index score (p = 0.011). Also, the changes in the distance on the 6-min walking test as well as B-type natriuretic peptide were significantly greater in the CABG + BMMNC group than in the control group. Conclusions In summary, patients with a previous MI and chronic heart failure could potentially benefit from isolated CABG (i.e., those who received CABG only) combined with BMMNCs delivered through a graft vessel. (Stem Cell Therapy to Improve Myocardial Function in Patients Undergoing Coronary Artery Bypass Grafting [CABG]; NCT00395811)

We have recently demonstrated the potential of (18)F-FDG as an imaging marker of myocardial ischemia if injected at peak exercise. However, how long increased (18)F-FDG uptake can be observed after an episode of exercise-induced myocardial ischemia is not known. We performed the current study to determine whether increased regional myocardial (18)F-FDG uptake at exercise in patients with coronary artery disease (CAD) persists on rest imaging (24 h later), after an episode of exercise-induced myocardial ischemia.Twenty-four patients with suspected CAD underwent exercise (99m)Tc-sestamibi and (18)F-FDG imaging. Repeated (18)F-FDG imaging was performed 24 h after exercise imaging, after an injection of a second dose of (18)F-FDG at rest in 20 patients. Perfusion imaging with (99m)Tc-sestamibi was simultaneously performed with (18)F-FDG imaging. All patients underwent coronary angiography.Eighteen patients had greater than or equal to 70% luminal narrowing of 1 or more coronary vessels. Fifteen patients (83%) showed increased regional (18)F-FDG uptake on exercise imaging, but only 11 patients (61%) had perfusion abnormalities. Of these 15 patients with increased regional (18)F-FDG uptake on exercise imaging, 8 (53%) had no discernible (18)F-FDG uptake, 5 (33%) had decreased (18)F-FDG uptake, and only 2 (13%) had persistent (18)F-FDG uptake on rest (18)F-FDG images. The summed (18)F-FDG uptake score significantly decreased, from 14.4 +/- 10.3 at exercise to 6.7 +/- 9.2 at rest (P = 0.01). Patients with persistent (18)F-FDG uptake at rest had more (18)F-FDG uptake and lower peak rate-pressure product at exercise, compared with patients with no residual (18)F-FDG uptake at rest.Exercise-induced regional myocardial (18)F-FDG uptake is highly specific and sensitive for exercise-induced myocardial ischemia. Regional myocardial (18)F-FDG uptake may persist 24 h after an episode of exercise-induced myocardial ischemia in some patients.

Aims To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium. Methods and results Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium. Conclusion Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.

BACKGROUND Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

The low cell engraftment after transplantation limits the successful application of stem cell therapy and the exact pathway leading to acute donor cell death following transplantation is still unknown. Here we investigated if processes involved in cell preparation could initiate downregulation of adhesion-related survival signals and further affect cell engraftment after transplantation. Human embryonic stem cell-derived endothelial cells (hESC-ECs) were suspended in PBS or Matrigel and kept at 4 °C. Quantitative RT-PCR analysis was used to test the adhesion and apoptosis genes’ expression of hESC-ECs. We demonstrated that cell detachment can cause downregulation of cell adhesion and extracellular matrix (ECM) molecules, but no obvious cell anoikis, a form of apoptosis after cell detachment, was observed. The downregulation of adhesion and ECM molecules could be regained in the presence of Matrigel. Finally, we transplanted hESC-ECs into a mouse myocardial ischemia model. When transplanted with Matrigel, the long-term engraftment of hESC-ECs was increased through promoting angiogenesis and inhibiting apoptosis and this was confirmed by bioluminescence imaging. In conclusion, ECM could rescue the functional genes expression after cell detached from culture dish and this finding highlights the importance of increasing stem cell engraftment by mimicking stem cell niches through ECM application.

1162 Objectives In 1925 Blumgart demonstrated that he could measure serial blood levels of isotope activity to determine cardiac contractility through the measurement of “circulation time.” Todays modern SPECT cameras replace the cloud chambers of Blumgarts era, allowing us the opportunity to measure serial changes in isotope concentration needed to measure ischemia. This study determines the clinical utility of Blumgarts method using todays SPECT camera. Methods One hundred twenty individuals underwent diagnostic study measuring changes in sestamibi activity in eight regions of interest (ROIs) using a SPECT camera. Subjects were stressed and using Blumgarts method of measuring isotope scintillations, serial measurements were compared in each of the eight regions with results found on coronary angiography. Results Parabolic regression of stenosis from coronary angiography (figure 1) on changes in isotope activity were compared for each of the vascular territories. The result yielded an effect size of R(95%)=0.72 to 0.95, p=3.8x10-8. Conclusions Prior investigations suggested that changes in isotope distribution over time could be employed to more accurately measure ischemia. A thorough literature search and investigation and application of Blumgarts method of serial measurements of isotope scintillation, when applied using todays SPECT camera reveals that changes in sestamibi distribution can be accurately measured, allowing clinicians to employee SPECT cameras to obtain angiographic results, while improving diagnostic accuracy and reducing patient radiation exposure. Research Support CVISM sponsored

Myocardial perfusion imaging (MPI), using radiotracers, has been in routine clinical use for over 40 years. This modality is used for the detection of coronary artery disease (CAD), risk stratification, optimizing therapy, and follow-up of patients with CAD. Molecular cardiovascular imaging using targeted radiotracers provides a unique opportunity for imaging biochemical and metabolic processes, and cell membrane transporter and receptor functions at a cellular and molecular level in experimental animal models as well as in humans. Cardiac imaging using radiolabeled free fatty acid analogues and glucose analogues enable us to image myocardial ischemia directly as an alternative to stress-rest MPI. Direct ischemia imaging techniques can avoid and overcome some of the limitations of standard stress-rest MPI. This article describes recent studies using (18) F-fluorodeoxyglucose ((18) FDG) for myocardial ischemia imaging.

Background —We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A 2A agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. Methods and Results —A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to 201 Tl (0.5 mCi) and 99m Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion ( P P P P P =NS), and transmural 201 Tl and 99m Tc-sestamibi count-activity ratios (0.48±0.11 and 0.51±0.09, respectively) were also comparable ( P =NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. Conclusions —CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of 201 Tl and 99m Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

OBJECTIVES The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl-201) scintigraphy. BACKGROUND Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution Tl-201 tomography before revascularization and a repeat resting echocardiogram ≥2 months later. RESULTS Global wall motion score index decreased from 2.38 ± 0.73 to 1.94 ± 0.82 after revascularization (p 0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a Tl-201 maximal uptake of ≥60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum Tl-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to Tl-201 scintigraphy. Importantly, a simple measurement of EDWT ≤0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Background —There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS. Methods and Results —We conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32±7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53±8 versus 52±9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group). Conclusions —Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.

Background —Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. Methods and Results —Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS P Conclusions —CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Background —Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure. Methods and Results —We evaluated 20 patients with coronary disease (64±13 years old, ejection fraction 28±7.5%) with DE (up to 40 μg · kg −1 · min −1 ), rest-redistribution 201 Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%, P P =0.03), and less interstitial fibrosis (2% versus 28%, P P P P =0.016), and higher thallium uptake (64% versus 35.5%, P P =0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis ( r =−0.83, P Conclusions —Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.

Objectives. We sought to study the accuracy of exercise perfusion scintigraphy in patients with an implanted apical right ventricular pacemaker. Background. The specificity of exercise perfusion scintigraphy is decreased in patients with a left bundle branch block. Patients with a permanent ventricular pacemaker have a similar conduction abnormality that may also potentially result in similar false positive perfusion defects. Methods. One hundred five patients with a right ventricular pacemaker underwent exercise thallium-201 tomography and coronary angiography within 7 days of each other. Patients with a previous myocardial infarction were excluded. Results. Patients were classified into four groups according to the agreement or disagreement between the thallium tomographic and coronary angiographic results. Only 8% of patients with normal results by both techniques were continuously paced during exercise, compared with 78% of patients with normal angiographic results but abnormal scintigraphic results. The mean defect size was 12% in the latter group. Most of the false positive defects were localized to the inferoposterior (71%), apical (50%) and inferoseptal (28%) walls. Conclusions. Patients who are paced in the right ventricular apex and who continue to be paced throughout exercise have a high incidence of false positive thallium-201 single-photon emission computed tomographic defects. (J Am Coll Cardiol 1997;29:1221–5)

Background Recent observations suggest that administration of nitrates before 201 Tl reinjection enhances the detection of reversible myocardial hypoperfusion. Methods and Results Ninety-six patients who underwent exercise-redistribution 201 Tl single photon emission computed tomography (SPECT) and had persistent defects at 4-hour redistribution imaging were prospectively randomized into a double-blind protocol in which they received a reinjection of 201 Tl (1.0 mCi) 5 minutes after either placebo or 0.8 mg sublingual nitroglycerin administration, followed by repeat SPECT imaging. Of the 69 patients who had coronary angiography, all except one had significant coronary stenoses. The overall extent of perfusion defect and the reversible component assessed by polar maps of the stress-redistribution images were similar in patients who received nitroglycerin or placebo. Among the 66 patients with persistent defects in the redistribution images, 58% of those receiving nitroglycerin showed improved reversibility after reinjection, compared with 33% of patients receiving placebo ( P P P Conclusions Nitrate-augmented 201 Tl reinjection significantly, albeit modestly, improves detection of defect reversibility, especially in patients with coronary collateral circulation.

PurposeVentricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.MethodsEighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.ResultsLV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both PConclusionDespite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.

Objectives. This study sought to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block.Backgroud. Patients with left bundle branch block often have septal perfusion defects during exercise perfusion tomography that mimic defects caused by coronary artery disease. These defects appear to be less frequent during pharmacologic stress using adenosine or dipyridamole. Data are scanty on the value of dobutamine tomography in these patients.Methods. We studied 383 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 5-year span. Perfusion tomography was performed in conjunction with exercise in 206 patients, adenosine in 127 and dobutamine in 50. Coronary angiography was performed within 1 month of the nuclear study in 77, 50 and 27 patients, respectively.Results. Exercise, adenosine and dobutamine tomography had similar sensitivity and specificity for the detection of >50% stenosis in the left circumflex (74% and 96%; 50% and 100%; 63% and 91%, respectively) and right coronary arteries (96% and 86%; 82% and 91%; 79% and 100%, respectively) and similar sensitivity for left anterior descending coronary artery stenosis (88%, 79% and 100%, respectively). However, the false-positive rate for septal defects was higher by exercise tomography (26 [46%] of 57) than by pharmacologic methods (5 [10%] of 48, p < 0.001), and there was no significant difference between adenosine (4 [11%] of 35) and dobutamine (1 [8%] of 13, p = 0.7). The specificity and predictive value of a positive test response for left anterior descending coronary artery stenosis were 36% and 51% for exercise compared with 81% and 85% for adenosine (p ≤ 0.001) and 80% and 90% for dobutamine (p < 0.05), respectively.Conclusions. In patients with left bundle branch block, pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients.

Background In a swine model of acute myocardial infarction (AMI), Statins can enhance the therapeutic efficacy of mesenchymal stem cell (MSCs) transplantation. However, the mechanisms remain unclear. This study aims at assessing whether atorvastatin (Ator) facilitates the effects of MSCs through activation of nitric oxide synthase (NOS), especially endothelial nitric oxide synthase (eNOS), which is known to protect against ischemic injury. Methods and Results 42 miniswines were randomized into six groups (n = 7/group): Sham operation; AMI control; Ator only; MSC only, Ator+MSCs and Ator+MSCs+NG-nitrol-L-arginine (L-NNA), an inhibitor of NOS. In an open-heart surgery, swine coronary artery ligation and reperfusion model were established, and autologous bone-marrow MSCs were injected intramyocardium. Four weeks after transplantation, compared with the control group, Ator+MSCs animals exhibited decreased defect areas of both “perfusion” defined by Single-Photon Emission Computed Tomography (−6.2±1.8% vs. 2.0±5.1%, P = 0.0001) and “metabolism” defined by Positron Emission Tomography (−3.00±1.41% vs. 4.20±4.09%, P = 0.0004); Ejection fraction by Magnetic Resonance Imaging increased substantially (14.22±12.8% vs. 1.64±2.64%, P = 0.019). In addition, indices of inflammation, fibrosis, and apoptosis were reduced and survivals of MSCs or MSC-derived cells were increased in Ator+MSCs animals. In Ator or MSCs alone group, perfusion, metabolism, inflammation, fibrosis or apoptosis were reduced but there were no benefits in terms of heart function and cell survival. Furthermore, the above benefits of Ator+MSCs treatment could be partially blocked by L-NNA. Conclusions Atorvastatin facilitates survival of implanted MSCs, improves function and morphology of infarcted hearts, mediated by activation of eNOS and alleviated by NOS inhibitor. The data reveal the cellular and molecular mechanism for anti-AMI therapy with a combination of statin and stem cells.

Stress echocardiography is mainly used in detection of coronary artery disease (CAD) and to assess risk. This study aimed to use adenosine stress echocardiography (ASE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to noninvasively assess coronary stenosis in patients with chest pain syndromes or anginal equivalent.NT-proBNP was measured after overnight fast in fifty patients, 42 males and 8 females, who were (57 ± 11) years old. They then underwent echocardiography before and during adenosine administration. Left ventricular (LV) diastolic function analyzed included mitral annular early (E') and late velocity (A') both at the mitral septal and lateral level and the mitral inflow to annulus ratio (E/E'). Coronary angiography was performed the following day after which patients were assigned to three groups: normal results (16 patients), stenosis 50% - 69% (17 patients) and stenosis ≥ 70% (17 patients).NT-proBNP levels in the groups of stenosis 50% - 69% and ≥ 70% were significantly higher than that in the group with normal results (P = 0.014 and P = 0.040). During adenosine stress, the E/E' in the group of stenosis ≥ 70% was higher than in the group of normal results (P = 0.024). E'(lateral)/A'(lateral) in the group of stenosis 50% - 69% and E'(septal)/A'(septal) and E'(lateral)/A'(lateral) in the group of stenosis ≥ 70% were also decreased during stress compared with baseline (P = 0.003, P = 0.001, P = 0.022). The variation of E'(septal)/A'(septal) before and during adenosine stress (ΔE'(septal)/A'(septal)) between the groups of normal results and stenosis ≥ 70% were significantly different (P = 0.001). By receiver operating characteristic (ROC), the specificity of ΔE'(septal)/A'(septal) ≥ 0.037 predicting coronary stenosis70% was 94%. The sensitivity and specificity of NT-proBNP ≥ 544.6 fmol/ml in predicting coronary stenosis ≥ 70% were 93% and 75%, respectively. NT-proBNP inversely correlated with E'(lateral)/A'(lateral) (r = - 0.390, P = 0.014) and positively correlated with E/E'(lateral) (r = 0.550, P = 0.001).Adenosine might induce diastolic dysfunction in patients with coronary stenosis more than 70% and NT-proBNP could reflect LV diastolic function to a certain extent. We support the prediction that most patients having chest pain syndromes or anginal equivalent with NT-proBNP544.6 fmol/ml and in ASE ΔE'(septal)/A'(septal) ≥ 0.037 might be spared coronary angiography.

Noninvasive cardiac imaging is now central to the diagnosis and management of patients with moderate probability for coronary artery disease. The aim of this study was to assess the impact of stress myocardial perfusion single photon emission computerized tomography (SPECT) on in-hospital coronary angiography and revascularization for such patients.Between January 2005 and June 2007, 1053 consecutive in-hospital patients (423 women, the average age of (57.2 ± 11.2) years) with suspected coronary artery disease but without any prior interventional treatment were retrospectively analyzed. All patients underwent a 2-day stress/rest (99m)Tc-methoxyisobutylisonitrile (MIBI) myocardial perfusion SPECT, including 984 exercise test and 69 adenosine test.Overall, stress/rest myocardial perfusion SPECT was normal in 973 patients (92.4%) and abnormal in 80 patients (7.6%). A total of 190 patients underwent coronary angiography, 46 underwent percutaneous coronary intervention and 10 coronary artery bypass grafting during hospitalization. From the whole perspective, only 14.7% of patients with normal SPECT underwent coronary angiography, so did 58.8% of patients with abnormal SPECT (χ(2) = 97.0, P0.001); furthermore, the rates of revascularization in patients with normal and abnormal SPECT were 2.8% and 36.3%, respectively (27 out of 973 vs. 29 out of 80, χ(2) = 157.9, P0.001). The extent and severity of ischemia did not add more predictive value for subsequent coronary angiography, but did have impact on revascularization. Multivariate analysis showed that reversible perfusion defect was the most predictive variable for referral rate to coronary angiography (odds ratio = 7.5, P0.001).Abnormal myocardial perfusion SPECT is a powerful referral for in-hospital coronary angiography and revascularization during the same hospitalization. Thus, stress/rest SPECT is an effective gatekeeper for early coronary angiography and invasive treatment for patients with suspected coronary artery disease.

Background The differentiation of constrictive pericarditis (CP) from restrictive cariomyopathy (RCM) is often difficult. This study sought to determine the clinical utility of cardiovascular magnetic resonance imaging (CMR) for differentiating both these disorders. Methods Twenty-three patients with surgically documented CP, 22 patients with RCM and 25 normal subjects were included in the study. CMR yielded information about cardiac morphology, function and tissue characteristics. The left (LA) and right atrial (RA) volume was calculated using the area-length method. The relative atrial volume ratio (RAR) was defined as the LA volume divided by RA volume. Receiver operating characteristic curve analysis was used to test the ability of different variables in differentiating CP from RCM. Results The maximal pericardial thickness in CP patients was significantly larger than in normal subjects and RCM patients. The RA volume index in RCM patients (90.5 ± 35.3 mL/m2) was significantly larger than in CP patients (71.4 ± 15.7 mL/m2, p = 0.006) and normal subjects (38.1 ± 9.0 mL/m2, p < 0.001). The LA volume index in RCM (96.0 ± 37.0 mL/m2) and CP patients (105.6 ± 25.1 mL/m2) was significantly larger than in normal subjects (39.5 ± 9.5 mL/m2, p < 0.001 for all). The RAR in CP patients (1.50 ± 0.29) was significantly larger than in RCM patients (1.12 ± 0.33, p < 0.001) and normal subjects (1.06 ± 0.20, p < 0.001). There were no differences between RCM patients and normal subjects in the RAR (p = 0.452). At a cut-off value of 1.32 for the RAR, the sensitivity was 82.6%, and the specificity was 86.4% in the detection of CP. Septal bounce was identified in 95.7% CP patients, in none of RCM patients and normal subjects. Late gadolinium enhancement (LGE) was present in 31.8% RCM patients and absence in all CP patients and normal subjects. Conclusions CMR with LGE and RAR can facilitate differentiation of CP from RCM.