Prognostic Value of Major Cardiac Event Risk Score Estimated With Gated Myocardial Perfusion Imaging in Japanese Patients With Coronary Artery Disease.

We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with ≥ 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for ≥ 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 ± 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease.

Effect of Asiasarum Root Extract and Its Constituents on Interleukin-1ß-Stimulated Matrix Metalloproteinase-1 Secretion from Human Gingival Fibroblasts.

Asiasarum root (roots and rhizome of Asiasarum sieboldii or A. heterotropoides var. mandshuricum) has been frequently used in traditional Chinese medicinal formulas for the management of oral malodor syndrome caused by periodontal disease. However, there are no scientific reports concerning these effects and the mechanism of action. The objective of this study was to examine the inhibitory effects of Asiasarum root and its constituents on oral malodor syndrome and periodontal disease. A 50% ethanolic extract of Asiasarum root (AR-ext) showed L-methionine γ-lyase (METase) inhibitory activity at a concentration of 200 µg/mL, and inhibited interleukin (IL)-1ß-stimulated matrix metalloproteinase (MMP)-1 secretion from human gingival fibroblasts (HGFs) at a concentration of 10 and 50 µg/mL without cytotoxic effects. Activity-guided fractionation of the AR-ext suggested that METase inhibitory activity was attributable to a mixture of linoleic and oleic acid, because these unsaturated fatty acids showed weak METase inhibitory activities. Similar fractionation using MMP-1 secretion inhibitory activity led to the isolation of two unsaturated fatty acid amides, (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (1) and (2E,4E,8Z,10Z)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), as active constituents with inhibitory activity on MMP-1 secretion from HGFs. To elucidate the inhibition mechanism on MMP-1 secretion, the effect of 2 on mitogen-activated protein kinase (MAPK) phosphorylation was examined. Western blotting analysis revealed that 2 (10 µM) reduced the phosphorylation of p38 and c-Jun-N-terminal kinase. These results suggested that 2 suppresses intracellular MMP-1 expression and MMP-1 secretion from IL-1ß-stimulated HGFs by down-regulation of MAPK phosphorylation.

Major cardiac event risk scores estimated with gated myocardial perfusion imaging in Japanese patients with coronary artery disease.

BACKGROUND: A Heart Risk Table has been reported as the first risk score based on nuclear cardiology to predict cardiac event rates in Japanese patients. However, there are no risk scores estimating risk of major cardiac events (MCEs) except severe heart failure. METHODS: We retrospectively investigated 2579 patients with known or suspected coronary artery disease (CAD) who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography between October 2004 and March 2011 and who had data on a 3-year follow-up. The perfusion images were analyzed with 20 segments of a five-point visual scoring model to estimate summed defect scores. The endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction and unstable angina pectoris. RESULTS: During the 3-year follow-up, 171 patients (6.6%) experienced MCEs comprising cardiac death (n=78), non-fatal myocardial infarction (n=30), and unstable angina pectoris (n=63). The multivariate logistic regression analysis indicated age, diabetes, estimated glomerular filtration rate (eGFR), and summed stress scores (SSS) as independent predictors of the MCEs and age, stress ejection fraction, eGFR, and SSS as independent predictors of cardiac death. Those four predictors and coefficients corresponding to them were used to make two different risk equations: MCE risk (%/3 years)=1/{1+Exp[-(-3.176+0.018×age+0.602×diabetes-0.022×eGFR+0.051×SSS)]}×100 and cardiac death risk (%/3 years)=1/{1+Exp[-(-2.602+0.031×age-0.031×eGFR+0.038×SSS-0.029×stress ejection fraction)]}×100. CONCLUSION: The risk scores obtained from this study are useful to predict MCEs in Japanese patients with CAD and are expected to be useful for management and informed consent of high-risk CAD patients.

Significance of worsening renal function and nuclear cardiology for predicting cardiac death in patients with known or suspected coronary artery disease.

BACKGROUND: Estimated glomerular filtration rates (eGFRs) at baseline are useful to determine the severity of renal function and to predict cardiac events. However, no studies aimed to demonstrate significance of eGFRs measured during follow-up and usefulness of combination with nuclear cardiology for prediction of cardiac death in patients with coronary artery disease (CAD). METHODS: We retrospectively investigated 1739 patients with known/suspected CAD who underwent myocardial perfusion single photon emission computed tomography (SPECT), who had eGFRs measured at baseline and after one year and who underwent a three-year follow-up. The SPECT images were analyzed with the visual scoring model to estimate summed defect scores. Reduction in eGFRs (ΔeGFR) was defined as the difference between eGFRs measured after one year and at baseline. The endpoint of the follow-up was cardiac deaths within three years after the SPECT, which were identified with medical records or responses to posted questionnaires. RESULTS: Cardiac death was observed in 54 of 1739 patients during the follow-up period (45.6±9.1 months). The multivariate Cox regression analysis showed baseline eGFRs, ΔeGFR, and summed stress scores to be significant independent variables for prediction of cardiac death. The area under receiver operating characteristic curves for detection of cardiac death was 0.677 for the baseline eGFR and 0.802 for the follow-up eGFR. Sensitivity of detection of cardiac death was significantly higher in the follow-up eGFR than in the baseline eGFR (p=0.0002). Combination of the best cut-off values, i.e. 9 for the summed stress scores and 10 for the ΔeGFR, which were suggested by receiver operating characteristic analysis, was useful for risk stratification of cardiac death both in patients with and without chronic kidney disease. CONCLUSION: Baseline and follow-up eGFRs as well as nuclear variables are useful to predict cardiac death in patients with known/suspected CAD.

Myocardial ischemic reduction evidenced by gated myocardial perfusion imaging after treatment results in good prognosis in patients with coronary artery disease.

BACKGROUND: There are no nuclear cardiology reports indicating the prediction of prognosis based on ischemic reduction after revascularization in Japanese patients with coronary artery disease (CAD). We aimed to evaluate quantitatively ischemia using myocardial perfusion single photon emission computed tomography (SPECT) before and after treatment such as revascularization and to determine a relationship between the ischemic reduction and the incidence of major cardiac events (MCEs) after the treatment in patients with CAD. METHODS: We retrospectively investigated 513 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion SPECT between October 2004 and March 2011 and who had a significant stenosis with 75% or greater narrowing of the coronary arterial diameter detected by coronary angiography performed after confirmation of ≥5% ischemia with SPECT. The patients underwent the treatment including revascularization and medication and thereafter were re-evaluated with SPECT during a chronic phase and followed up to confirm prognosis for ≥1 year. The follow-up period was 33.4±16.4 months. The endpoint was the incidence of the MCEs consisting of cardiac death, non-fatal myocardial infarction, and unstable angina pectoris. RESULTS: During the follow-up, 45 patients experienced MCEs comprising cardiac death (n=13), non-fatal myocardial infarction (n=3), and unstable angina pectoris (n=29). The multivariate Cox proportional hazards regression model analysis for the risk of the MCEs showed the changes in the summed difference score % (p=0.0102) and the stress left ventricular ejection fraction after the treatment (p=0.0146) as significant independent variables. The incidence of the MCEs significantly decreased in the patients with ≥5% ischemic reduction than in the patients without ≥5% ischemic reduction and in the patients without residual ischemia than in the patients with the residual ischemia. CONCLUSION: Myocardial ischemic reduction detected by nuclear cardiology leads to a decrease in MCE rates after treatment in Japanese patients with CAD.

Usefulness of automated assessment of nuclear cardiology for prediction of major cardiac events in Japanese patients with known or suspected coronary artery disease: comparison with conventional visual assessment in a large-scale prognostic study.

BACKGROUND: There are no reports indicating that automated quantification with a total perfusion deficit (TPD) is used to predict future cardiac events in Japanese patients. We, therefore, aimed to determine the prognostic value of the automated assessment with the TPD for risk stratification of major cardiac events (MCEs) in Japanese patients with known or suspected coronary artery disease (CAD). METHODS: We retrospectively investigated 2848 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2008. The follow-up period was 25.8 ± 11.0 months. The TPD was automatically derived from the SPECT image through the QPS software with the Japanese normal database. Twenty segments of SPECT images were analyzed with the 5-point visual scoring model to estimate summed scores. The endpoint of the follow-up was the occurrence of MCEs within 1 year after the SPECT, which were identified with medical records or responses to a posted questionnaire. RESULTS: During the first year of the follow-up, 62 patients had MCEs, which comprised cardiac death (n = 30), non-fatal myocardial infarction (n = 13), and unstable angina pectoris (n = 19). The MCE rates positively correlated with the stress TPD and the summed stress score. Sensitivity of the automated quantification with the TPD for detection of the MCEs was high and similar to that of the visual semi-quantification. Multivariate Cox regression analysis indicated that significant independent predictors for the MCEs were an estimated glomerular filtration rate and the ischemic variables both in the automated quantification and visual semi-quantification. CONCLUSION: The automated quantification with the TPD is useful for prognostic risk stratification of MCEs in Japanese patients with known or suspected CAD. Its predictive power is similar to that of the visual semi-quantification by expert interpreters.

Validation of automated quantification of nuclear cardiology in Japanese patients using total perfusion deficits: Comparison with visual assessment.

BACKGROUND: Automated quantitative assessment based on a total perfusion deficit (TPD) has been recognized to be useful for detection of coronary artery disease (CAD). We, therefore, aimed to validate reproducibility of the automated quantification with the TPD on myocardial perfusion single photon emission computed tomography (SPECT) images in Japanese patients with history of stable CAD. METHODS: Patients (n=47, age 67 ± 10) underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion SPECT on two separate occasions with the same protocol within 3-26 months. They had abnormal findings on the first SPECT imaging by visual analysis and had no changes in symptoms, cardiac medications, coronary risk factors, and electrocardiogram findings at the time of the second imaging. They had no intervening coronary revascularization and myocardial infarction between the first and second imaging. The TPD was automatically derived from SPECT images through quantitative perfusion SPECT software with the Japanese normal database. A visual summed stress score (SSS) was estimated with the 5-point visual scoring model for 20 segments of SPECT images by independent expert interpreters. Abnormal criteria for the stress TPD and SSS were defined as ≥5% and ≥4, respectively. RESULTS: The stress TPD determined by the quantitative analysis well correlated between the first and second imaging (r=0.985) as well as the SSS by the visual analysis showed good correlation (r=0.978). The correlation coefficients were similar between the visual and quantitative analyses. Bland-Altman analyses indicated extremely good reproducibility in both assessments. CONCLUSION: The TPD is evidently a quantitative index having high reproducibility and the automated quantification with it provides comparable results to the visual assessment by experienced interpreters. The automated quantification with the TPD is highly significant for clinical assessment of CAD, and allows easily performing myocardial perfusion SPECT imaging without expert interpreters.

Diagnostic value of automated quantification of nuclear cardiology in Japanese patients with single vessel coronary artery disease: comparison between Japanese and American normal databases.

BACKGROUND: The Japanese diagnostic assessment of nuclear cardiology has usually been based on semi-quantitative visual analyses but not on automated quantification with a total perfusion deficit (TPD). We, therefore, aimed to determine whether automated TPD quantification is useful to detect coronary artery disease (CAD) in Japanese patients in comparison with conventional visual segmental analysis, and to compare results from the automated assessment between the Japanese and American normal databases (NDBs). METHODS: Patients with suspected CAD underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) and coronary angiography within three months. The TPD was automatically derived from the SPECT image through quantitative perfusion SPECT software with the Japanese and American NDBs. The visual summed stress scores (SSS) were estimated with the 5-point visual scoring model for 20 segments of SPECT images. An abnormal criteria for the stress TPD and SSS were defined as ≥ 5% and ≥ 4, respectively. RESULTS: Detection sensitivity of CAD was 87% with the stress TPD score derived from the Japanese NDB and 85% with the SSS in visual analysis. In contrast, the detection sensitivity with the stress TPD score derived from the American NDB was 75%, which was significantly lower than that with the Japanese TPD (p=0.0004). Specificity of the automated Japanese TPD assessment was similar to that of the visual SSS assessment (87% vs. 80%). Thus, sensitivity and specificity of the automated quantitative assessment based on the TPD scores derived from the Japanese NDB were consistent with that of visual quantification based on the segmental defect scores. CONCLUSION: The automated quantitative assessment with the Japanese NDB is useful for the detection of CAD when experts in visual interpretation of a myocardial perfusion SPECT image were absent in a clinical setting.

Risk stratification of cardiovascular events in patients at all stages of chronic kidney disease using myocardial perfusion SPECT.

BACKGROUND: Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Therefore, stratification of the prognostic risk of cardiovascular events is useful for their clinical management. We evaluated the ability of electrocardiogram (ECG)-gated myocardial perfusion single photon emission computed tomography (SPECT) to predict cardiac events among Japanese patients at all stages of CKD including those on hemodialysis. METHODS: Patients with CKD undergoing ECG-gated myocardial perfusion SPECT to investigate suspected ischemic heart disease were followed up to monitor retrospectively major cardiac events including cardiac death, non-fatal myocardial infarction, and unstable angina pectoris. Summed stress score, summed rest score, and summed difference score were estimated with a 20 segment 5-point scoring model. The severity of CKD was divided into five levels based on estimated glomerular filtration rate (eGFR) revised for the Japanese population. RESULTS: The follow-up period was 25.8 ± 11.0 months. Sixty-two major cardiac events (cardiac death, n=30; non-fatal myocardial infarction, n=13; unstable angina pectoris, n=19) developed in 2243 patients during the first year of follow-up. The findings of multivariate Cox proportional hazards regression analysis indicated that diabetes, eGFR, the summed difference score, and summed stress score were significant independent predictors of cardiac events. The major cardiac event rate at one year increased in proportion to the progression of CKD stage. The major cardiac event-free survival rate decreased steeply over time in patients with CKD stage 5 compared with those who had CKD stages 4 or less. CONCLUSION: Myocardial perfusion SPECT can contribute to the prediction of cardiac events and survival in patients at all stages of CKD including those on hemodialysis.