Hirokazu Ohigashi

Role of FDG PET-CT in Takayasu arteritis: sensitive detection of recurrences.

OBJECTIVES The aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases. BACKGROUND The clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment. METHODS Thirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects. RESULTS The max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p < 0.001 each). Given a max SUV cutoff of 2.1, sensitivity for active-phase TA was 92.6%, specificity 91.7%, positive predictive value 96.2%, and negative predictive value 84.6%. In receiver-operating characteristic curves comparison, max SUV was superior to C-reactive protein (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). Max SUV was significantly higher in relapsing on treatment cases (n = 17) than in stable on treatment cases (n = 12) (median value, 2.6 vs. 1.9; p < 0.001). CONCLUSIONS FDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity.

Quantitative Measures of Coronary Stenosis Severity by 64-Slice CT Angiography and Relation to Physiologic Significance of Perfusion in Nonobese Patients: Comparison with Stress Myocardial Perfusion Imaging

Coronary stenosis severity by 64-slice CT angiography (CTA) is acceptably correlated with intravascular ultrasound. Stress myocardial perfusion imaging using SPECT is an established method for assessment of the functional significance of coronary stenosis. Our aim was to assess a clinical validation of quantitative measurements of coronary stenosis severity by 64-slice CTA and the relation to the physiologic significance of myocardial perfusion. Methods: One hundred four patients with suspected coronary artery disease underwent 64-slice CTA and stress 201Tl SPECT. The stenosis severities of 105 coronary lesions assessed by CTA with sufficient image quality were compared with the results of stress 201Tl SPECT. The body mass index (BMI) of the patients was 23.8 kg/m2 (range, 21.1–25.6 kg/m2). Results: Reversible defects began to increase progressively when the area of stenosis was at least 60%, and the prevalence of these reversible defects and their severity significantly increased as the degree of stenosis increased. When stenosis severity by CTA is < 60%, ischemia is seldom observed; when stenosis severity is ≥80%, ischemia is common (86%). For intermediate stenosis severity values of 60%–70%, the prevalence of reversible defects was 9 of 27 vessels (33%), and for stenosis severity values of 70%–80%, the prevalence was 20 of 37 vessels (54%). When evaluating the diagnostic accuracy of stenosis severity by CTA to identify patients with ischemia excluding all nonevaluable vessels, applying stenosis thresholds of >70% results in 79% sensitivity, 92% specificity, 66% positive predictive value, and 96% negative predictive value. A lesion minimal luminal cross-sectional area of < 3.7 mm2 was a good accurate cutoff value for significant coronary narrowing using stress SPECT, with a sensitivity of 88% and specificity of 83% by receiver-operating-characteristic analysis. Conclusion: Despite an excellent negative predictive value to rule out the presence of ischemia, 64-slice CTA alone is a poor discriminator of the functional significance of myocardial ischemia in a highly selected patient population with a low BMI.

Adiponectin protects against doxorubicin-induced cardiomyopathy by anti-apoptotic effects through AMPK up-regulation

AIMS Adiponectin (APN) has been reported to protect against ischaemia-reperfusion injury and hypertrophy. However, few reports have investigated the cardioprotective effects of APN in doxorubicin (DOX)-induced cardiomyopathy; therefore, we studied the cardioprotective mechanisms of APN in this model. METHODS AND RESULTS In an in vivo study, we quantified the cardiac pathohistology of C57BL/6 mice [wild-type (WT) mice], APN transgenic mice with high APN concentrations [APN transgenic sense (SE) mice], and those with reduced APN concentrations [APN transgenic antisense (AS) mice] after intraperitoneal injections of DOX (4 mg/kg) weekly for 6 weeks. The survival rate after 14 days was significantly increased in APN-SE mice (WT vs. APN-AS vs. APN-SE: 40 vs. 17 vs. 73%, P < 0.05). We assessed myocardial pathohistological changes and observed that fibrosis and apoptosis were significantly decreased in APN-SE mice compared with those of the other groups. We also assessed DOX-induced apoptotic mechanisms in vitro using cultured cardiomyocytes isolated from neonatal WT mice. The expression of adenosine monophosphate-activated protein kinase (AMPK) and anti-apoptotic factor Bcl-2 increased, but that of pro-apoptotic factor Bax decreased in cardiomyocytes treated with highly concentrated APN. The protective effects of APN were reversed by the addition of an AMPK inhibitor (dorsomorphin) to the culture medium. CONCLUSION These data suggest that APN improved cardiac function through anti-apoptotic effects by up-regulation of AMPK in DOX-induced cardiomyopathy in mice.

Early validation study of 64-slice multidetector computed tomography for the assessment of myocardial viability and the prediction of left ventricular remodelling after acute myocardial infarction

AIMS We aim to validate the ability of multidetector computed tomography (MDCT) for assessing myocardial viability and predicting left ventricular (LV) remodelling after acute myocardial infarction (AMI). METHODS AND RESULTS In 52 consecutive patients with first AMI, 64-slice MDCT without iodine re-injection was performed immediately following coronary stenting. Electrocardiogram-gated thallium-201 single-photon emission tomography was performed using QGS programs within 5 days and 6 months after onset. Among the 52 patients, 18 patients (Group A) showed transmural contrast-delayed enhancement on MDCT images, 20 patients (Group B) showed subendocardial contrast-delayed enhancement, and 14 patients (Group C) had no contrast-delayed enhancement. In the acute phase, peak creatine kinase-MB [497 (189-744), 182 (90-358), 85 (40-204) IU/mL, respectively, P = 0.0004] was significantly higher in Group A, while the incidence of myocardial blush grade 3 (22, 67, 75%, respectively, P = 0.001) and LV ejection fraction (41 +/- 7, 53 +/- 12, 62 +/- 11%, respectively, P < 0.0001) were significantly lower in Group A. During the 6-month period, LV remodelling (P = 0.001) and the number of rehospitalization for heart failure (P = 0.0017) were more significantly observed in Group A. CONCLUSION Myocardial contrast-delayed enhancement patterns provide promising information regarding myocardial viability, LV remodelling, and prognosis in AMI.

Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity

Aims The assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI) is a useful tool, but the clinical utility of late gadolinium enhancement (LGE) in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis. Methods and Results We enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19) and Inactive disease (n = 30) groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR), SNR increment (post-SNR minus pre-SNR), pre- and post-contrast contrast-to-noise ratios (CNR), and CNR increment (post-CNR minus pre-CNR) were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease. Conclusion Contrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.

Impact of Smoking on Coronary Microcirculatory Resistance in Patients With Coronary Artery Disease

The aim of this study was to investigate the relationship between coronary microvascular function and smoking using the 3 parameters fractional flow reserve (FFR), coronary flow reserve (CFR(thermo)), and index of microcirculatory resistance (IMR) in patients with coronary artery disease (CAD). A total of 97 CAD patients with 148 intermediate stenotic lesions were divided into two groups: current and former smokers (Smokers: n = 54), and those who had never smoked (Non-smokers: n = 43). Coronary physiology measurements were made following coronary angiography at rest and during hyperemia induced with intravenous adenosine triphosphate. If a patient had several intermediate lesions, the lesion producing the largest IMR value and minimum FFR(myo) and CFR(thermo) value was selected. Averaged over all patients, the FFR(myo), CFR(thermo), and IMR values were 0.86 ± 0.10, 2.66 ± 1.50, and 20.8 ± 10.7, respectively. There was no significant correlation between FFR(myo) and IMR. There were no significant differences between smokers and non-smokers in FFR(myo) value (median: 0.85 [IQR: 0.74-0.90] versus 0.87 [IQR: 0.83-0.90], P = 0.15) and CFR(thermo) value (median: 1.90 [IQR: 1.56-3.16] versus 2.10 [IQR: 1.50-2.67] U, P = 0.95). The IMR value was significantly greater in smokers (median: 24.2 [IQR: 16.8-32.5] U versus 18.5 [IQR: 15.4-27.0] U, P = 0.04). In multivariate analysis, smoking was an independent predictor of increased IMR. Smoking appears to have a detrimental effect on coronary microvascular function as measured by IMR.

Effects of immunosuppressive and biological agents on refractory Takayasu arteritis patients unresponsive to glucocorticoid treatment

BACKGROUND We aimed to investigate the effects of immunosuppressive and biological agents on refractory Takayasu arteritis (TA) patients resistant to or dependent on glucocorticoids. METHODS Forty-four consecutive TA patients were enrolled, and the clinical characteristics and effectiveness of the immunosuppressive and biological agents in achieving and maintaining remission among glucocorticoid-resistant or glucocorticoid-dependent patients were investigated. RESULTS Fifteen patients showed favorable response to the initial glucocorticoid treatment, and 29 patients exhibited resistance to initial glucocorticoid treatment or relapsed with tapering glucocorticoid. Of the 29 patients, 5 responded to additional glucocorticoid treatment, and 22 of the remaining 24 glucocorticoid-resistant or glucocorticoid-dependent patients were prescribed immunosuppressive agents. Methotrexate was the most commonly used in these patients as the first-line treatment. In total, 10 patients maintained remission using immunosuppressive agents, with the effectiveness of each agent about 20%. The only significant difference between patients who were and were not able to achieve and maintain remission with immunosuppressive agents was the presence of the HLA-B52 allele (p<0.0001). Biological agents were administered to 6 patients refractory to immunosuppressive agents. All patients were administered tumor necrosis factor (TNF) inhibitors as the first-line treatment, and 3 patients maintained remission. Anti-interleukin-6 receptor antibody was administered to 2 patients who were resistant to the TNF inhibitors, and 1 patient achieved and maintained remission. CONCLUSION In our cohort, 64% of the glucocorticoid-resistant or glucocorticoid-dependent patients maintained remission through a combined treatment with glucocorticoid, immunosuppressive agents, and/or biological agents. The combined use of immunosuppressive and biological agents appears to be a promising treatment option for achieving and maintaining remission in refractory TA patients.