Prediction of cardiovascular events using myocardial strain ratio derived from 13N-ammonia positron emission tomography.

OBJECTIVES: Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH3-PET), can predict the prognosis of patients with various heart diseases. We aimed to investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR. METHODS: Ninety-five patients underwent NH3-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (p = 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59-33.7, p = 0.011). CONCLUSIONS: MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD. KEY POINTS: • We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone. • MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease. • MSR is a potential new indicator of revascularization.

First Validation of Myocardial Flow Reserve Derived from Dynamic 99mTc-Sestamibi CZT-SPECT Camera Compared with 13N-Ammonia PET.

13N-ammonia positron emission tomography (NH3-PET) can evaluate myocardial blood flow (MBF) at rest, stress, and myocardial flow reserve (MFR) as well as the ratio of MBF at stress to that at rest. MFR is useful in predicting the prognoses of patients with various heart diseases. Cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) enables us to acquire dynamic images of radiotracer kinetics and measure original MBF and MFR using 99mTc-sestamibi. This study aimed to investigate the utility of CZT-SPECT for quantitative assessment of MBF compared to NH3-PET. We validated the correlation of MBF and MFR between CZT-SPECT and NH3-PET. Fourteen patients using one-day rest/stress CZT-SPECT, D-SPECT followed by NH3-PET within 1 month were enrolled and analyzed prospectively. The reproducibility of the MBF and MFR obtained with these two methods was examined using Spearman's correlation coefficient and Bland-Altman plot analysis. The diagnostic value of D-SPECT for abnormal MFR defined using NH3-PET results as MFR < 2.0 was assessed using receiver-operating characteristic (ROC) analysis. The median duration between D-SPECT and NH3-PET was 20 days. Although MBF was overestimated by D-SPECT compared to NH3-PET at high value (mean difference, 0.43 [0.34-0.53]), MBF and MFR were correlated with the two modalities (MBF: r = 0.71, P < 0.0001, MFR: r = 0.60, P < 0.0001). The ROC curve analysis demonstrated a cutoff of 1.6 for detecting abnormal MFR with D-SPECT (sensitivity, 68%; specificity, 91%; AUC, 0.75). MBF and MFR obtained using D-SPECT and NH3-PET had a good correlation, suggesting that the quantitative MFR evaluation by CZT-SPECT may help understand the trend of NH3-PET MFR.

Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET.

BACKGROUND: We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS. METHODS AND RESULTS: CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan-Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4. CONCLUSIONS: BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.

Prognostic study of cardiac events in Japanese patients with chronic kidney disease using ECG-gated myocardial Perfusion imaging: Final 3-year report of the J-ACCESS 3 study.

BACKGROUND: Myocardial perfusion imaging (MPI) is considered useful for risk stratification among patients with chronic kidney disease (CKD), without renal deterioration by contrast media. METHODS AND RESULTS: The Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS 3) is a multicenter, prospective cohort study investigating the ability of MPI to predict cardiac events in 529 CKD patients without a definitive coronary artery disease. All patients were assessed by stress and rest MPI with 99mTc-tetrofosmin and data were analyzed using a defect scoring method and QGS software. Major cardiac events were analyzed for 3 years after registration. The mean eGFR was 29.0 ± 12.8 (mL/minute/1.73 m2). The mean summed stress/rest/difference (SSS, SRS, SDS) scores were 1.9 ± 3.8, 1.1 ± 3.0, and 0.8 ± 1.8, respectively. A total of 60 cardiac events (three cardiac deaths, six sudden deaths, five nonfatal myocardial infarctions, 46 hospitalization cases for heart failure) occurred. The event-free survival rate was lower among patients with kidney dysfunction, higher SSS, and higher CRP values. Multivariate Cox regression analysis independently associated SSS ≥8, eGFR <15 (mL/minute/1.73 m2), and CRP ≥0.3 (mg/dL) with cardiac events. CONCLUSIONS: Together with eGFR and CRP, MPI can predict cardiac events in patients with CKD.

Diagnostic accuracy of an artificial neural network compared with statistical quantitation of myocardial perfusion images: a Japanese multicenter study.

PURPOSE: Artificial neural networks (ANN) might help to diagnose coronary artery disease. This study aimed to determine whether the diagnostic accuracy of an ANN-based diagnostic system and conventional quantitation are comparable. METHODS: The ANN was trained to classify potentially abnormal areas as true or false based on the nuclear cardiology expert interpretation of 1001 gated stress/rest 99mTc-MIBI images at 12 hospitals. The diagnostic accuracy of the ANN was compared with 364 expert interpretations that served as the gold standard of abnormality for the validation study. Conventional summed stress/rest/difference scores (SSS/SRS/SDS) were calculated and compared with receiver operating characteristics (ROC) analysis. RESULTS: The ANN generated a better area under the ROC curves (AUC) than SSS (0.92 vs. 0.82, p < 0.0001), indicating better identification of stress defects. The ANN also generated a better AUC than SDS (0.90 vs. 0.75, p < 0.0001) for stress-induced ischemia. The AUC for patients with old myocardial infarction based on rest defects was 0.97 (0.91 for SRS, p = 0.0061), and that for patients with and without a history of revascularization based on stress defects was 0.94 and 0.90 (p = 0.0055 and p < 0.0001 vs. SSS, respectively). The SSS/SRS/SDS steeply increased when ANN values (probability of abnormality) were >0.80. CONCLUSION: The ANN was diagnostically accurate in various clinical settings, including that of patients with previous myocardial infarction and coronary revascularization. The ANN could help to diagnose coronary artery disease.

Introduction of nuclear medicine research in Japan.

There were many interesting presentations of unique studies at the Annual Meeting of the Japanese Society of Nuclear Medicine, although there were fewer attendees from Europe than expected. These presentations included research on diseases that are more frequent in Japan and Asia than in Europe, synthesis of original radiopharmaceuticals, and development of imaging devices and methods with novel ideas especially by Japanese manufacturers. In this review, we introduce recent nuclear medicine research conducted in Japan in the five categories of Oncology, Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that this article will encourage the participation of researchers from all over the world, in particular from Europe, in scientific meetings on nuclear medicine held in Japan.

Diagnosis and Detection of Myocardial Injury in Active Cardiac Sarcoidosis--Significance of Myocardial Fatty Acid Metabolism and Myocardial Perfusion Mismatch.

BACKGROUND: Myocardial injury can be detected more sensitively using (123)I-radioiodinated 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) than thallium-201 (TL). The present study investigated whether (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake as an index of active inflammation in patients with cardiac sarcoidosis (CS) is associated with BMIPP and TL findings, and whether dual single-photon emission computed tomography (SPECT) can facilitate diagnosis of CS. METHODS AND RESULTS: We retrospectively enrolled 52 consecutive patients with suspected CS who were assessed on FDG-PET/computed tomography (CT) and BMIPP/TL dual SPECT. The SPECT images were divided into 17 segments and then BMIPP and TL total defect scores (BMDS, TLDS) as well as mismatch scores (BMDS-TLDS: sumMS) were calculated. Maximum standardized uptake value (SUVmax) in the entire myocardium was obtained from FDG-PET/CT. SUVmax was much higher in patients with, than without CS (P<0.0001). BMDS was higher and sumMS much higher in CS (P<0.05 and P<0.0001, respectively). The sensitivity and specificity of sumMS to detect CS were 74% and 80%, respectively. SUVmax was not associated with either BMDS or sumMS in the patients with CS. On multivariate analysis, the combination of sumMS and SUVmax had greater prognostic significance compared with each parameter on its own. CONCLUSIONS: BMIPP and TL dual-tracer mismatch is a useful finding to diagnose CS, and adds greater diagnostic value to SUVmax on FDG-PET/CT.

A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging.

PURPOSE: Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. METHODS: The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF.

Myocardial perfusion imaging for predicting cardiac events in Japanese patients with advanced chronic kidney disease: 1-year interim report of the J-ACCESS 3 investigation.

PURPOSE: Whether myocardial perfusion imaging (MPI) can predict cardiac events in patients with advanced conservative chronic kidney disease (CKD) remains unclear. METHODS: The present multicenter prospective cohort study aimed to clarify the ability of MPI to predict cardiac events in 529 patients with CKD and estimated glomerular filtration rates (eGFR) < 50 ml/min per 1.73(2) without a definitive diagnosis of coronary artery disease. All patients were assessed by stress-rest MPI with (99m)Tc-tetrofosmin and analyzed using summed defect scores and QGS software. Cardiac events were analyzed 1 year after registration. RESULTS: Myocardial perfusion abnormalities defined as summed stress score (SSS) ≥4 and ≥8 were identified in 19 and 7 % of patients, respectively. At the end of the 1-year follow-up, 33 (6.2 %) cardiac events had occurred that included cardiac death, sudden death, nonfatal myocardial infarction, and hospitalization due to heart failure. The event-free rates at that time were 0.95, 0.90, and 0.81 for groups with SSS 0-3, 4-7, and ≥8, respectively (p = 0.0009). Thus, patients with abnormal SSS had a higher incidence of cardiac events. Multivariate Cox regression analysis showed that SSS significantly impacts the prediction of cardiac events independently of eGFR and left ventricular ejection fraction. CONCLUSION: MPI would be useful to stratify patients with advanced conservative CKD who are at high risk of cardiac events without adversely affecting damaged kidneys.

13N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease.

BACKGROUND: Ischemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. 13N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). METHODS: Overall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET. RESULTS: PMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan-Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13-8.15; p < 0.0001). CONCLUSIONS: PMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.

Risk Stratification Using Right Ventricular Longitudinal Strain Ratio Derived from 13N-Ammonia PET in Patients with Ischemic Heart Disease.

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia (13N-NH3) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13N-NH3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.

Prediction of cardiac allograft vasculopathy using splenic switch-off on myocardial PET.

BACKGROUND: Heart transplantation (HTx) is a definitive therapy for refractory heart failure. Cardiac allograft vasculopathy (CAV), characterized by diffuse arteriopathy involving the epicardial coronary arteries and microvasculature, is the major cause of death for patients with HTx. 13 N-ammonia positron emission tomography (NH3-PET) can offer diagnostic and prognostic utility for CAV. The splenic switch-off (SSO) detected in NH3-PET is a hemodynamic indicator of favorable response to adenosine. We hypothesized that both CAV and SSO reflected a pathology that progresses in parallel with systemic vascular endothelial dysfunction. Therefore, we quantitatively evaluated splenic adenosine reactivity measured using NH3-PET as an index of endothelial function, and examined its predictability for CAV. METHODS: Forty-eight patients who underwent NH3-PET after HTx were analyzed. The spleen ratio was calculated as the mean standardized uptake value, measured by placing an ROI on the spleen, at stress divided by that at rest. SSO was defined by a cutoff determined using receiver operating characteristic (ROC) analysis for the spleen ratio. The endpoint was appearance or progression of CAV. Predictability of SSO was analyzed using Kaplan-Meier analysis. RESULTS: The endpoint occurred in 9 patients during a mean follow-up of 45 ±â€¯17 months. ROC curve analysis demonstrated a cutoff of 0.94 for spleen ratio. Patients without SSO displayed a significantly higher CAV rate than those with SSO (p = 0.022). CONCLUSIONS: SSO reflects the endothelial function of systemic blood vessels and was a predictor of CAV in patients with HTx.

Association between abnormal myocardial fatty acid metabolism and cardiac-derived death among patients undergoing hemodialysis: results from a cohort study in Japan.

BACKGROUND: Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (ß-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years). PREDICTOR: Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4). OUTCOMES: Cardiac-derived death, including cardiac and sudden death. MEASUREMENTS: HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors. RESULTS: Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P < 0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009). LIMITATIONS: Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed. CONCLUSIONS: Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population.

Myocardial Strain Derived from 13N-ammonia Positron Emission Tomography: Detection of Ischemia-Related Wall Motion Abnormality.

Background: Due to the limitation of spatial resolution, cardiac nuclear medicine images have not been applied to feature-tracking method to automatic extraction of myocardial contours. We have successfully applied the feature-tracking method to high-resolution cine 13N-ammonia positron emission tomography (PET) images to calculate the regional myocardial strains. Here, we investigate the potential of 13N-ammonia PET-derived strain to detect ischemia-related wall motion abnormality. Methods: Data of adenosine-stress/rest 13N-ammonia PET for 95 coronary artery disease patients was retrospectively analyzed. Using an original algorithm dedicated to 13N-ammonia PET, the longitudinal strain (LS) corresponding to the three main coronary artery territories [right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex coronary artery (LCX)] was calculated from semi-automatic endocardial contours extraction on cine 13N-ammonia PET images of the left ventricular long-axis. The presence of ischemia in three main territories was determined from rest and stress-perfusion images. Results: In all three coronary territories, LS at stress was significantly smaller at rest in the ischemic region RCA: -19.2±8.0% vs. -22.7±6.1%, LAD: -19.0±6.9% vs. -24.4±6.4%, LCX: -20.5%±7.6% vs. -22.6±6.9%). In contrast, in the non-ischemic region, there was no significant difference between the LS at stress and at rest. Receiver-operating-characteristic analysis revealed that using the optimal cutoff of the LS ratio of stress to rest, ischemia could be diagnosed with area under the curve of 0.82 in the RCA, 0.86 in the LAD, and 0.69 in the LCX. Conclusions: Myocardial strain derived from endocardial feature-tracking of 13N-ammonia PET cine imaging is reduced in the ischemia induced by adenosine-stress. The LS ratio of stress to rest may detect wall motion abnormality related to ischemia.

Prognostic Implications of Sarcoidosis Granulomas　- Insights From the Multicenter Registry, the Japanese Cardiac Sarcoidosis Prognostic Study.

Background: Definitions of cardiac sarcoidosis (CS) differ among guidelines. Any systemic histological finding of CS is essential for the diagnosis of CS in the 2014 Heart Rhythm Society statement, but not necessary in the Japanese Circulation Society 2016 guidelines. This study aimed to reveal the differences in outcomes by comparing 2 groups, namely CS patients with or without systemic histologically proven granuloma. Methods and Results: This study retrospectively included 231 consecutive patients with CS. CS with granulomas in ≥1 organs was diagnosed in 131 patients (Group G), whereas CS without any granulomas was diagnosed in the remaining 100 patients (Group NG). Left ventricular ejection fraction (LVEF) was significantly reduced in Group NG compared with Group G (44±13% vs. 50±16%, respectively; P=0.001). However, Kaplan-Meier curves showed that major adverse cardiovascular events (MACE)-free survival outcomes were comparable between the 2 groups (log-rank P=0.167). Univariable analyses showed that significant predictors of MACE were Groups G/NG, histological CS, LVEF, and high B-type natriuretic peptide (BNP) or N-terminal pro BNP concentrations, but none of these was significant in multivariable analyses. Conclusions: Overall risks of MACE were similar between the 2 groups despite different manifestations in cardiac dysfunction. The data not only validate the prognostic value of non-invasive diagnosis of CS, but also show the need for careful observation and therapeutic strategy in patients with CS without any granuloma.

Prognostic value of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography in diabetic patients with suspected ischemic heart disease.

BACKGROUND: Because of their high risk for cardiovascular events, we investigated the role of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) SPECT in evaluating the prognosis of diabetic patients with suspected coronary heart disease. METHODS AND RESULTS: We retrospectively registered 186 diabetic patients with suspected coronary heart disease, but no previous diagnosis of heart disease, who had been examined by BMIPP and thallium (TL) dual SPECT. They were followed for over 2 years. The dual SPECT images were scored to obtain summed defect scores for each SPECT image (BMDS, TLDS and mismatch score [MS]). The primary endpoint was the first incidence of all-cause cardiac events. The secondary endpoint was cardiac death. Clinical classical risk factors in addition to the stage of chronic kidney disease (CKD), as well as cardiac function, were included in the prognostic analysis. Cardiac events occurred in 39 patients, including 8 cardiac deaths. Kaplan-Meier analysis revealed significantly more frequent cardiac event rates in patients with than without MS ≥5 or BMDS ≥6 (P<0.0001). Cox hazard multivariate analysis showed that MS and CKD stage or BMIPP and CKD stage were independent predictors. Only hemodialysis was a significant prognostic indicator for cardiac death. CONCLUSIONS: BMIPP SPECT when combined with CKD stage accurately predicts cardiac events among diabetic patients with suspected ischemic heart disease.

Association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan.

BACKGROUND: There is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial. We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan. METHODS: From the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests (Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study), 1205 patients managed with SPECT were stratified by 10 % myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year. RESULTS: Patients with ≥10 % myocardial ischemia (n = 173) were less likely to be women than patients with <10 % myocardial ischemia (n = 1032) and had a significantly higher 1-year cumulative incidence of MACEs (6.9 % vs. 1.8 %, p < 0.0001). After adjusting for confounders, the risk of ≥10 % myocardial ischemia relative to <10 % myocardial ischemia for MACEs remained significant [adjusted hazard ratio (95 % confidence interval), 2.40 (1.09-5.26), p = 0.029]. After adjusting including treatments, the risk of MACEs became insignificant between the ≥10 % myocardial ischemia group and the <10 % myocardial ischemia group [adjusted hazard ratio (95 % confidence interval), 1.04 (0.45-2.45), p = 0.92]. CONCLUSION: The presence of ≥10 % myocardial ischemia at diagnosis was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease.

Myocardial Flow Reserve in Coronary Artery Disease with Low Attenuation Plaque: Coronary CTA and 13N-ammonia PET Assessments.

RATIONALE AND OBJECTIVES: Physiological measurements from coronary angiography show that coronary stenosis with necrotic core plaque reduces coronary flow reserve (CFR). Myocardial flow reserve (MFR) estimated by 13N-ammonia PET (NH3-PET) is a different index from CFR. Low attenuation plaque (LAP) on coronary CTA (CCTA) contains necrotic core, but the link between LAP and MFR has not been elucidated. We aimed to investigate the influence of LAP on MFR in coronary artery disease (CAD). MATERIALS AND METHODS: The study included 105 consecutive patients who underwent NH3-PET and CCTA within 3 months. Nonevaluable coronary arteries due to severe calcification and stent implants were excluded. Finally, 290 major vessels were retrospectively analyzed. Coronary arteries were divided into mild (1%-49%), moderate (50%-69% stenosis), and severe (≥70% stenosis) groups. Coronary plaques were classified either LAP (including soft tissue CT value <30 HU) or completely classified plaques. MFR for the major vessels were calculated and MFR <2.0 was considered a significant decrease. Comparison of MFR between territories with and without LAP, and the effect of plaque characteristics on MFR was analyzed. RESULTS: MFR was significantly lower for territories with LAP than with calcified plaques or no plaque (2.1 ± 0.7, 2.4 ± 0.7, and 2.3 ± 0.7; p < 0.05). There was no difference between calcified plaque and no plaque territories (p = 0.79). Multivariate logistic analysis for plaque characteristics and stenosis severity revealed that LAP and severe stenosis were independent predictors for territories with MFR <2.0 with odds ratios of 3.1 (95% confidence interval, 1.2-8.1) and 3.0 (95% confidence interval, 1.7-5.3). CONCLUSION: LAP reduced MFR compared with calcified plaque or no plaque in CAD. LAP is an independent predictor of the territory with MFR <2.0.

Imaging of Heart Type Fatty Acid Binding Protein Under Acute Reperfusion Ischemia Using Radio-labeled Antibody in Rat Heart Model.

Purpose: Heart-type fatty acid binding protein (H-FABP) is primary transporter of free fatty acid and plays an important role in myocardial metabolism, which is characterized by high specificity and rapid appearance under ischemic condition. The objective of this study was to clarify the usefulness of imaging study of targeting H-FABP appearance using radio-labeled antibody, and correlation with myocardial fatty acid metabolism and perfusion in acute reperfusion ischemia. Method: Wistar rats were allotted to sham-operated control group (sham; n=4), ischemia non-reperfused group (IG; n=5), and ischemia-reperfusion group (RG; n=5). Ligation of left coronary artery (LCA) was performed for IG and RG. 20 min of ischemia was followed by 60min of reperfusion for RG. 125I labeled anti H-FABP antibody (anti H-FABP), BMIPP and 99mTc-sestamibi (MIBI) was injected intravenously. Multi-tracer digital autoradiogram was performed using µ-imager®. The ratio of radioactivity in LCA related (culprit) area to the inferior (remote) area (target uptake ratio=TUR) was generated. Results: In sham group, no visually detectable accumulation was observed for the anti H-FABP image, and TURMIBI and TURBMIPP were equivalent to 1. In IG, TURMIBI and TURBMIPP were remarkably low (0.12±0.01, 0.24±0.07). In RG, TURMIBI was significantly lower (0.20±0.03, p<0.05 vs. other groups). However, TURBMIPP was significantly higher (2.78±1.28, p<0.05) compared to the sham and IG, whereas anti H-FABP showed markedly higher ratio in the reperfused area compared to the sham and IG (3.43±0.73 vs. 0.31±0.13 and 1.09±0.07 for IG and sham; p<0.05, and <0.01, respectively). Conclusion: Anti H-FABP accumulated specifically in reperfused area under acute ischemia, and it accorded to the area where fatty acid metabolism was activated. This study has shown the future potential for clinical application in vivo imaging of acute coronary syndrome.