Evaluation of cardiac magnetic resonance imaging parameters to detect anatomically and hemodynamically significant coronary artery disease.

BACKGROUND: Cardiac magnetic resonance (cMR) perfusion imaging is a promising technique to assess coronary artery disease (CAD). Our objective was to evaluate accuracy of various cMR imaging parameters to detect significant CAD as compared with angiography or fractional flow reserve (FFR). METHODS: We prospectively enrolled 37 patients who underwent coronary angiography, FFR, and cMR perfusion imaging. Semiquantitative assessments, namely maximum up-slope and peak-intensity indexes, were derived from time-intensity ratios between rest and stress. Myocardial perfusion reserve (MPR), calculated using Fermi deconvolution technique, was the quantitative cMR imaging parameter. Qualitative assessments were visually performed by independent analysts. Accuracy of quantitative, semiquantitative, and qualitative cMR imaging data was compared with quantitative coronary angiography in 108 segments and FFR in 44 segments. RESULTS: Sensitivity and specificity for hemodynamically significant CAD (FFR < or = 0.75) were 92.9% and 56.7%, respectively, for MPR (cutoff, 2.06). Area under the curve to detect FFR < or = 0.75 was 0.78 for MPR (P < .01), 0.63 for up-slope (P = NS), and 0.66 (P = NS) for peak intensity. Sensitivity and specificity for anatomically significant CAD (> 50% diameter stenosis [DS]) were 87.2% and 49.2%, respectively, for MPR (cutoff, 2.06). Area under the curve was 0.75 for MPR, 0.69 for up-slope, and 0.65 for peak intensity to detect > 50% DS (all P < .05). Visual assessment yielded sensitivity of 78.6% and specificity of 65.5% to predict FFR < or = 0.75 and sensitivity of 74.5% and specificity of 67.2% to predict > 50% DS. CONCLUSIONS: Myocardial perfusion reserve appears to be the most accurate index to detect anatomical and hemodynamically significant CAD. Standardization of such quantitative methods, with minimal operator dependency, would be useful for clinical and research applications.

Tea catechins improve left ventricular dysfunction, suppress myocardial inflammation and fibrosis, and alter cytokine expression in rat autoimmune myocarditis.

BACKGROUND: Myocarditis is a clinically serious disease. Tea catechins have been shown to reduce inflammation; however the effects of catechins on the development of myocarditis have not been well studied. AIMS: To clarify the role of catechins, using an experimental autoimmune myocarditis (EAM) model. METHODS AND RESULTS: Lewis rats were immunized with porcine cardiac myosin to establish EAM. Tea catechins were administered orally from day 0 to day 21 (Group A, n=12), from day 14 to day 21 (Group B, n=8), or saline (Group C, n=9) daily. Rats were killed on day 21. Echocardiograms indicated that Group A showed significantly improved cardiac function compared to Group C. Pathologically, non-treated EAM hearts showed severe myocardial cell infiltration and fibrosis; however Group A showed significantly less area. Immunohistochemistry revealed enhanced expression of NF-kappaB and ICAM-1 in non-treated EAM hearts, which was suppressed by catechin administration in Group A. mRNA levels of TNF-alpha were decreased and Th2 cytokines were markedly enhanced in Group A compared with the control group. Late catechin administration (Group B) showed limited effects on EAM. CONCLUSION: The catechins suppressed ventricular remodelling in EAM; thus catechin treatment might be a promising option for the prevention of EAM myocarditis.

Hepatocyte growth factor ameliorates the progression of experimental autoimmune myocarditis: a potential role for induction of T helper 2 cytokines.

Hepatocyte growth factor (HGF) plays a role in cell protection, antiapoptosis, antifibrosis, and angiogenesis. However, the role of HGF in the immune system is not well defined. We examined the influence of HGF on T cells and the effects of HGF therapy in acute myocarditis. Lewis rats were immunized on day 0 with cardiac myosin to establish experimental autoimmune myocarditis (EAM). Human HGF gene with hemagglutinating virus of the Japan-envelope vector was injected directly into the myocardium on day 0 or on day 14 (two groups of treated rats). Rats were killed on day 21. Expression of c-Met/HGF receptor in splenocytes and myocardial infiltrating cells was confirmed by immunohistochemical staining or FACS analysis. Myocarditis-affected areas were smaller in the treated rats than in control rats. Cardiac function in the treated rats was markedly improved. An antigen-specific T cell proliferation assay was done with CD4-positive T cells isolated from control rats stimulated with cardiac myosin. HGF suppressed T cell proliferation and production of IFN-gamma and increased production of IL-4 and IL-10 secreted from CD4-positive T cells in vitro. Additionally, TUNEL assay revealed that HGF reduced apoptosis in cardiomyocytes. HGF reduced the severity of EAM by inducing T helper 2 cytokines and suppressing apoptosis of cardiomyocytes. HGF has potential as a new therapy for myocarditis.

Hepatocyte growth factor: Effects on immune-mediated heart diseases.

There is growing evidence of the potential role of hepatocyte growth factor (HGF) in various cardiovascular diseases. In addition to the beneficial effects of HGF in myocardial infarction, heart failure, and occlusive peripheral arterial disease, administration of HGF effectively suppresses acute and chronic cardiac allograft rejection and autoimmune myocarditis. The present review summarizes recent advances in the utility of HGF for heart diseases, especially immune-mediated heart diseases. Possible mechanisms of action in the suppression of T-cell-mediated immunity are also discussed.

Blockade of the interaction between PD-1 and PD-L1 accelerates graft arterial disease in cardiac allografts.

BACKGROUND: Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS AND RESULTS: C57BL/6 murine hearts were transplanted into B6.C-H2KhEg mice for examination of GAD. PD-L1 was expressed in SMCs of the thickened intima in the graft coronary arteries, and administration of anti-PD-L1 monoclonal antibody (mAb) enhanced the progression of GAD (luminal occlusion: 55+/-5.0% versus 9.8+/-4.3%, P<0.05). The expressions of interferon gamma (IFN-gamma) and tumor necrosis factor alpha of cardiac allografts were upregulated in response to anti-PD-L1 mAb treatment. In vitro, PD-L1 expression was induced in SMCs in response to IFN-gamma stimulation. Sensitized splenocytes increased SMC proliferation, and anti-PD-L1 mAb in combination with IFN-gamma stimulation increased this proliferation. CONCLUSIONS: The PD-L1 pathway regulates both the proliferation of SMCs and GAD. Thus, control of this interaction is a promising strategy for suppression of GAD.

Attenuation of graft arterial disease by manipulation of the LIGHT pathway.

OBJECTIVE: The tumor necrosis factor (TNF) superfamily member LIGHT, which binds herpes virus entry mediator (HVEM) and lymphotoxin beta receptor (LTbetaR), plays important roles in regulating the immune response. To clarify the mechanism underlying graft arterial disease (GAD), we investigated the role of the LIGHT pathway in the progression of GAD. METHODS AND RESULTS: Hearts from Bm12 mice were transplanted into C57BL/6 (B/6) mice (class II mismatch). Recipients were injected intraperitoneally with HVEMIg (100 microg per treatment) every 7 days for 8 weeks. Treatment with HVEMIg significantly attenuated GAD (luminal occlusion=16.5+/-7.7% versus control allograft=62.6+/-12.1%, P<0.05), and significantly decreased intragraft IL-4, IL-6, and interferon-gamma (IFN-gamma) mRNA expression compared with controls. LTbetaR was expressed in smooth muscle cells (SMCs) with or without cytokine stimulation, whereas HVEM was detected in SMCs stimulated by IFN-gamma. Coculture of SMCs with T cells after transplantation induced SMC proliferation, and addition of HVEMIg resulted in inhibition of SMC proliferation. CONCLUSIONS: These results indicate that the LIGHT pathway plays important roles in the regulation not only of T-cell activation but also of SMC proliferation. Blockade of the LIGHT pathway is a promising avenue for the prevention of GAD.

HMG-CoA reductase inhibitor attenuates experimental autoimmune myocarditis through inhibition of T cell activation.

OBJECTIVE: This study tested the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor affects T cell-mediated autoimmunity through inhibition of nuclear factor-kappaB (NFkappaB) and reduces the severity of experimental autoimmune myocarditis (EAM). METHODS: EAM was induced in Lewis rats by immunization with myosin. High-dose or low-dose fluvastatin or vehicle was administered orally for 3 weeks to rats with EAM. RESULTS: Fluvastatin reduced the pathophysiological severity of myocarditis. Fluvastatin inhibited expression of NFkappaB in the nuclei of myocardium in EAM. Fluvastatin reduced production of Th1-type cytokines, including interferon (IFN)-gamma and interleukin (IL)-2, and inhibited expression of inflammatory cytokine mRNAs in the myocardium. Infiltration of CD4-positive T cells into the myocardium and T cell proliferative responses were suppressed by fluvastatin. Plasma lipid levels did not differ between the groups. CONCLUSIONS: Fluvastatin ameliorates EAM by inhibiting T cell responses and suppressing Th1-type and inflammatory cytokines via inactivation of nuclear factor-kappaB, and this activity is independent of cholesterol reduction.

Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway.

OBJECTIVE: Inducible costimulator (ICOS) is a member of the CD28 family. Although inflammation is an essential pathological feature of myocarditis, the role of ICOS in myocarditis remains unclear. METHODS AND RESULTS: Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoimmune myocarditis (EAM). Flow cytometry was used to examine expression of ICOS on myocardial infiltrating cells. Anti-ICOS antibody or ICOS-immunoglobulin (ICOSIg) was administered intravenously, and rats were killed on day 14 or 21 to study effects of ICOS/ICOS-ligand (ICOSL) pathway blockade during the antigen priming phase (days 0-14) or immune response phase (days 14-21), respectively. The heart weight to body weight ratio was determined, and histological examination and echocardiogram were performed to evaluate the severity of the disease. Cytokine expression in the heart and T cell proliferation against cardiac myosin were analyzed. Flow cytometry revealed that the majority of infiltrating cells, especially CD4-positive cells, expressed ICOS. Blockade of the ICOS/ICOSL pathway during the immune response phase attenuated EAM development. However, blockade of the ICOS/ICOSL pathway during the antigen priming phase did not attenuate and exacerbate EAM. Blockade of T cell activation through ICOS suppressed expression of cytokines including INF-gamma, IL-4, IL-6, IL-10, IL-1 beta, and TNF-alpha and inhibited T cell proliferation in vitro. CONCLUSIONS: Blockade of T cell activation through ICOS during the immune response phase regulates development of EAM, and therefore, ICOS may be an effective target for treating myocarditis.

Gene therapy for heart transplantation-associated acute rejection, ischemia/reperfusion injury and coronary arteriosclerosis.

Acute cardiac allograft rejection is still a major complication after heart transplantation. Acute rejection usually responds to conventional immunosuppressants, however, the nonspecific nature of the immunosuppression and the toxicities of the drugs can be life threatening and may compromise the recipient's quality of life. In addition, cardiac allograft arteriosclerosis or chronic rejection limits the long-term survival of recipients. Such conditions cannot be prevented with conventional therapies. To overcome acute and chronic rejection of cardiac allograft as well as ischemia/reperfusion injury associated with organ preservation many novel approaches have been proposed. Gene transfection of the donor organ during organ preservation is an attractive method, because the transfected genes would not affect recipients and treatment could be delivered specifically to the site of inflammation. This method could be useful to prevent graft failure without systemic adverse effects. Here we shall review current advances in gene therapies to prevent and treat organ failure of transplanted allografts.

Diagnostic accuracy of quantitative cardiac MRI evaluation compared to stress single-photon-emission computed tomography.

BACKGROUND: Cardiac MRI (cMRI) perfusion is a promising non-invasive tool to assess myocardial ischemia. The accuracy of quantitative cMRI perfusion has been recently demonstrated, but to date no previous study has compared this technique with stress single-photon-emission computed tomography (SPECT). The aim of this study was to evaluate the diagnostic accuracy of myocardial perfusion reserve (MPR) based on cMRI compared with SPECT. METHODS: We examined 24 patients who underwent coronary angiography, stress SPECT and cMRI perfusion. Qualitative assessment of both SPECT and cMRI images, quantification of cMRI perfusion, and quantitative coronary angiography (QCA) were independently performed. MPR was calculated using Fermi deconvolution technique. Accuracy of quantitative and qualitative data was examined to detect > 50% diameter stenosis (DS) by QCA. RESULTS: Qualitative analysis was obtained in 198 segments and quantitative analysis was performed in 171 segments. Significant coronary artery disease (CAD) was present in 81.8% of patients. Visual cMRI assessment yielded sensitivity of 74.4% and specificity of 79.4% to predict > 50%DS, while SPECT showed sensitivity of 67.4% and specificity of 81.3%. The sensitivity for SPECT in the right coronary artery territory and apex was low compared to cMRI. Sensitivity and specificity for detection of significant CAD were 89.5% and 46.6% for MPR (cutoff 1.92). Area under the curve was 0.75 for MPR (P < 0.01). CONCLUSIONS: The diagnostic accuracy of qualitative examination of perfusion cardiac MRI and stress SPECT were comparable. The high sensitivity and low operator dependency of quantitative cMRI makes it an attractive tool to evaluate myocardial perfusion.

Variable histological and ultrasonic characteristics of restenosis after drug-eluting stents.

Bare-metal stents have undergone intense pathological and clinical examination, but histological characterization of drug-eluting stent (DES) restenosis (ISR) remains unknown. We report a series of cases (n=6) with intravascular ultrasound (IVUS) and pathological examinations over 8 months after DES deployment. Tissue samples were obtained using atherectomy devices in 5 cases and a thrombectomy catheter in 1 case. Histology revealed not only smooth muscle cell proliferation, which correlated with homogeneous hypoechoic tissue by IVUS in one case, but also demonstrated delayed healing features such as organized fibrin deposition in 3 cases (one with homogeneous echolucent tissue by IVUS), macrophage and T-lymphocyte infiltration in others. IVUS appearance of ISR components varied from echolucent to echodense images. This report suggests a variable histological and IVUS pattern of ISR after DES implantation. Further investigations are necessary to define the potentially pro-thrombotic histological features of ISR after DES implantation, and the relationship between the molecular mechanisms of thrombosis and DES restenosis.

Angiographic and 3D intravascular ultrasound assessment of overlapping bare metal stent and three different formulations of drug-eluting stents in patients with diabetes mellitus.

OBJECTIVES: The aim of this study was to examine the impact of overlapping bare-metal stent (BMS) and three different formulations of drug-eluting stent (DES) on intimal hyperplasia (IH) response of patients with diabetes mellitus (DM). METHODS: Forty-nine DM patients treated with overlapping BMS (19 lesions), sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8 lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and 9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) analysis were performed in the entire stented segment and in the overlapped (OL) and non-overlapped (non-OL) subsegments. Clinical outcomes were evaluated at 1-year follow-up. RESULTS: Post-procedure (PO-) QCA measurements were similar in all stent groups, and between OL and non-OL subsegments in each individual type of stents. Percent IH was lower in SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type of DES groups. SES showed significantly less %IH compared with PES and TES in OL and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in all type of DES and BMS groups. There were no aneurysm formation and no stent thrombosis up to 1-year follow-up. CONCLUSIONS: Overlapping BMS is associated with enhanced IH response in diabetic patients, whereas overlapping DES, particularly SES and PES, appear effective to inhibit IH without detectable late vascular adverse effects.

Attenuation of autoimmune myocarditis in rats by mesenchymal stem cell transplantation through enhanced expression of hepatocyte growth factor.

Mesenchymal stem cells (MSCs) have various effects, including angiogenic, myogenic, and paracrine actions. In this study, we determined whether MSC transplantation attenuates experimental autoimmune myocarditis (EAM). The mechanisms involved were also investigated. Male Lewis rats were immunized with myosin to establish EAM on day 0. MSCs, isolated from isogenic rats, were injected directly into the myocardium on day 14 (group MSC-2W), day 21 (group MSC-3W), or day 28 (group MSC-4W). In the MSC transplantation groups, cardiac systolic function detected by echocardiography was significantly improved, the EAM affected area determined by histological examination was significantly decreased, and capillary density was increased compared to that in the control groups. Expression of hepatocyte growth factor protein was enhanced by MSC transplantation. MSC transplantation inhibited myocardial expression of interleukin-2, -6, and -10 mRNAs. MSC transplantation reduces the severity of EAM by inducing neovascularization and inhibiting inflammatory cytokine production. Enhanced expression of hepatocyte growth factor was associated with these effects. Autoimmune myocarditis may be a good clinical target for MSC transplantation.

Quantitative contrast enhanced magnetic resonance imaging for the evaluation of peripheral arterial disease: a comparative study versus standard digital angiography.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of semiautomated analysis of contrast enhanced magnetic resonance angiography (MRA) in patients who have undergone standard angiographic evaluation for peripheral vascular disease (PVD). BACKGROUND: Magnetic resonance angiography is an important tool for evaluating PVD. Although this technique is both safe and noninvasive, the accuracy and reproducibility of quantitative measurements of disease severity using MRA in the clinical setting have not been fully investigated. METHODS: 43 lesions in 13 patients who underwent both MRA and digital subtraction angiography (DSA) of iliac and common femoral arteries within 6 months were analyzed using quantitative magnetic resonance angiography (QMRA) and quantitative vascular analysis (QVA). Analysis was repeated by a second operator and by the same operator in approximately 1 month time. RESULTS: QMRA underestimated percent diameter stenosis (%DS) compared to measurements made with QVA by 2.47%. Limits of agreement between the two methods were +/- 9.14%. Interobserver variability in measurements of %DS were +/- 12.58% for QMRA and +/- 10.04% for QVA. Intraobserver variability of %DS for QMRA was +/- 4.6% and for QVA was +/- 8.46%. CONCLUSIONS: QMRA displays a high level of agreement to QVA when used to determine stenosis severity in iliac and common femoral arteries. Similar levels of interobserver and intraobserver variability are present with each method. Overall, QMRA represents a useful method to quantify severity of PVD.

Quantitative magnetic resonance perfusion imaging detects anatomic and physiologic coronary artery disease as measured by coronary angiography and fractional flow reserve.

OBJECTIVES: To evaluate the ability of quantitative perfusion cardiac magnetic resonance (CMR) to assess the hemodynamic significance of coronary artery disease (CAD) compared with well-established anatomic and physiologic techniques. BACKGROUND: Fractional flow reserve (FFR) is considered by many investigators to be a reliable stenosis-specific method to determine hemodynamically significant CAD. Quantitative perfusion CMR is a promising noninvasive approach to detect CAD but has yet to be validated against FFR. METHODS: This is a prospective study in patients with suspected CAD who underwent coronary angiography, FFR, and CMR assessments. The quantitative myocardial perfusion reserve (MPR) was calculated in 720 myocardial sectors (8 sectors/slice). The MPR was calculated from the ratio between stress and rest myocardial flow based on signal intensity time curves using deconvolution analysis. Stress was simulated with adenosine for both FFR and MPR. The MPR assessments were compared to FFR (n = 44 coronary segments) and quantitative coronary angiography (n = 108 segments) in the corresponding coronary territories. RESULTS: The MPR was 1.54 +/- 0.36 in segments with FFR < or =0.75 (n = 14) and 2.11 +/- 0.68 in those with FFR >0.75 (n = 30; p = 0.0054). An MPR cutoff of 2.04 was 92.9% (95% CI 77.9 to 100.0) sensitive and 56.7% (95% CI 32.8 to 80.6) specific in predicting a coronary segment with FFR < or =0.75. The MPR was 1.54 +/- 0.49 in coronary segments with > or =50% diameter stenosis (DS) (n = 47) and 2.13 +/- 0.80 in segments with <50% DS (n = 61; p < 0.001). An MPR cutoff of 2.04 was 85.1% (95% CI 71.1 to 99.2) sensitive and 49.2% (95% CI 33.6 to 64.8) specific in predicting CAD with > or =50% DS. CONCLUSIONS: Quantitative perfusion CMR is a safe noninvasive test that represents a stenosis-specific alternative to determine the hemodynamic significance of CAD.

A cyclooxygenase-2 inhibitor alters Th1/Th2 cytokine balance and suppresses autoimmune myocarditis in rats.

Acute myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. Cyclooxygenase (COX)-2 is a key factor for progression of inflammation. Although inflammation is an essential pathological feature of acute myocarditis, the role of COX-2 in this process remains unclear. Thus, the purpose of this study was to clarify the role of COX-2 in acute myocarditis. We used a rat experimental autoimmune myocarditis (EAM) model and a specific COX-2 inhibitor in this study. Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. We administered the COX-2 inhibitor (meloxicam, 0.1 mg/kg per day) daily; the rats were killed on day 21. Echocardiograms, body and heart weight, heart rate, blood pressure, and histological and molecular examinations were performed. Cytokine expression in the hearts and cell proliferation against cardiac myosin were also analyzed. The COX-2 inhibition during the immune response (late) phase attenuated EAM development; however, the inhibition during the antigen priming (early) phase did not attenuate EAM. The COX-2 inhibitor altered Th1/Th2 cytokine balance and inhibited cell proliferation in vitro. The COX-2 inhibitor suppresses the development of EAM. COX-2 regulation is promising for treating acute myocarditis.

"Head-to-head comparison between sirolimus-eluting and paclitaxel-eluting stents in patients with complex coronary artery disease: an intravascular ultrasound study".

BACKGROUND: The aim of this study was to assess neointimal hyperplasia following sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) implantation in a patients with complex coronary disease. METHOD: Between January to December 2004, 70 patients were enrolled in this study (SES = 37; PES = 33. The primary objective was to assess the efficacy of SES and PES on neointimal proliferation inhibition in patients with complex coronary lesions by volumetric 3D intravascular ultrasound (IVUS) assessment at six-month follow-up. RESULTS: Baseline clinical, demographic or angiographic characteristics were well balanced in both groups. All procedures as well as hospitalisation were uneventful. The percentage of B2/C lesions in our study was > 90% in both groups. The IVUS-assessed in-stent mean neointimal hyperplasia volume was significantly lower in lesions treated with SES compared to PES (4.1 +/- 11 mm3 vs. 17.4 +/- 23 mm3, p < 0.002) at 6 month follow-up. No difference in both MACE (3.0 versus 6.0%, p = NS) and restenosis (5.4 versus 9.1%, p = NS) were found. The in-segment late loss at six month was 0.26 mm in the SES and 0.48 mm in the PES group (p = NS). CONCLUSIONS: The present study showed reduced neointimal proliferation after sirolimuseluting as compared to paclitaxel-eluting stents in patients with complex coronary artery disease. Both SES and PES were associated with low rate of angiographic restenosis or major adverse cardiovascular events.

A CCR1 antagonist prevents the development of experimental autoimmune myocarditis in association with T cell inactivation.

Chemokines play an important role in induction of chemotaxis of immune cells. CCR1 is a chemokine receptor expressed on neutrophils, monocytes, and T lymphocytes. The role of CCR1 in immunity is not well examined. We demonstrated the role of CCR1 on T lymphocytes and the effect of a CCR1 antagonist, BX471 in myocarditis. Lewis rats were immunized with cardiac myosin on day 0 to establish experimental autoimmune myocarditis. Rats were then administered BX471 subcutaneously every day (group BX0: n = 7) or from day 14 (group BX14: n = 7) and were killed on day 21. We confirmed expression of CCR1 in cells infiltrating the myocardium by immunohistochemistry and FACS analysis. The development of myocarditis was almost completely prevented in group BX0, and myocarditis-affected areas were significantly decreased in size in group BX14. Cardiac function was markedly improved. Ribonuclease protection assay showed that the CCR1 antagonist treatment suppressed mRNA expression for IL-6, IL-1beta, and TNF-alpha in the hearts. An antigen-specific T cell proliferation assay was performed with CD4-positive T cells isolated from control rats immunized with cardiac myosin. T cell proliferation was inhibited by the CCR1 antagonist. Additionally, we showed by Western blot that the CCR1 antagonist suppressed ERK1/2 and JNK activities in T cells stimulated with myosin and that IL-2 reversed this suppression. The CCR1 antagonist reduced the severity of EAM by inhibiting cytokine expression and inducing T cell inactivation. Thus, the CCR1 antagonist may provide a novel therapeutic strategy treatment of myocarditis.

Utility of gallium-67 scintigraphy for evaluation of cardiac sarcoidosis with ventricular tachycardia.

BACKGROUND: The outcome of cardiac sarcoidosis is sometimes very poor. Ventricular tachycardia (VT) associated with cardiac sarcoidosis is the most common cause of sudden death among most patients. However, there is no established method for potential VT in patients with cardiac sarcoidosis. Thus, we investigated the utility of evaluation of gallium-67 scintigraphy for potential VT in patients with cardiac sarcoidosis. METHODS AND RESULTS: Cardiac sarcoidosis was diagnosed in 25 patients at ours or collaborating hospitals during the period 1982 through 2004. Twenty-one of these patients were treated with corticosteroid, and these patients were divided into two groups, depending on whether VT was present: a non-VT group (n=7) and a VT group (n=14). Laboratory and gallium-67 scintigraphy findings were examined in both groups. During the follow-up period, initial and maintenance dosages of corticosteroid did not differ significantly between the groups. Accumulation of gallium-67 in the heart at the time of diagnosis was detected more frequently in the VT group than in the non-VT group (14.3 vs. 71.4%, p<0.05). Six of the seven VT patients who underwent follow-up examination showed improvement on the scintigram obtained after treatment. Five of the six showed no VT recurrence in terms of Holter electrocardiogram, electrophysiologic study, or delivery of implantable cardioverter defibrillator shock. Serum angiotensin-converting enzyme and lysozyme concentrations were within normal limits in most patients in both groups. CONCLUSIONS: Activity of sarcoid granulomas may be associated with the occurrence of VT. Gallium-67 scintigraphy reflects the activity of sarcoid granulomas and thus is useful for evaluation of cardiac sarcoidosis in patients with potential VT.

Characterization of plaque prolapse after drug-eluting stent implantation in diabetic patients: a three-dimensional volumetric intravascular ultrasound outcome study.

OBJECTIVES: The aim of this research was to evaluate the plaque prolapse (PP) phenomenon after bare-metal (BMS) and drug-eluting stent (DES) implantation in patients with diabetes mellitus using 3-dimensional volumetric intravascular ultrasound (IVUS). BACKGROUND: Plaque prolapse has been observed in up to 22% of patients treated with BMS. Diabetic patients have a larger atherothrombotic burden and may be more prone to have PP. However, the incidence of PP and its clinical impact after DES implantation is unknown. METHODS: Three-dimensional IVUS was performed after intervention and at 9-month follow-up in 168 patients with diabetes (205 lesions) treated with bare BX Velocity stents ((BX Velocity/Sonic, Cordis, Johnson & Johnson) (BMS, n = 65), sirolimus-eluting stents (Cypher, Cordis) (SES, n = 69), and paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts) (PES, n = 71). Intravascular ultrasound data at the sites of PP were compared with stented segments without PP in each lesion. Outcomes were evaluated at 9- and 12-month follow-up. RESULTS: There were 42 sites of PP (BMS = 11, SES = 11, PES = 20, p = NS) in 34 stented segments of 205 (16.6%) lesions. Plaque prolapse was more frequent in the right coronary artery and in chronic total occlusion lesions. Post-procedure PP volume was 1.95 mm3 in BMS, 2.96 mm3 in SES, and 4.53 mm3 in PES. At follow-up, tissue volume increased at PP sites in both BMS and PES, but not after SES. Neointimal proliferation was similar between PP and non-PP sites. Stent thrombosis and restenosis rates were similar between PP and non-PP lesions. CONCLUSIONS: The incidence of PP after implantation of new generation tubular stents in patients with diabetes remains high. Drug-eluting stent implantation was not associated with increased risk of PP. Plaque prolapse was not associated with stent thrombosis or increased neointimal proliferation.