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.

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.

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.

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.

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.

Multicenter Registry in the Japanese Cardiac Sarcoidosis Prognostic (J-CASP) Study: Baseline Characteristics and Validation of the Non-invasive Approach Using 18F-FDG PET.

Background: Recent advances in cardiac modalities contribute to the guidelines on the diagnosis of cardiac sarcoidosis (CS) updated by the Japanese Circulation Society. The multicenter registry, Japanese Cardiac Sarcoidosis Prognostic (J-CASP) study tried to reveal recent trends of diagnosis and outcomes in CS patients and to validate the non-invasive diagnostic approach, including cardiac 18F-fluorodeoxyglucose (FDG) study. Methods/results: Databases from 12 hospitals consisting of 231 CS patients (mean age, 64 years; female, 65%; LV ejection fraction, 47%) diagnosed by the guidelines with FDG positron emission tomography (PET) study were integrated to compile clinical information on the diagnostic criteria and outcomes. Cardiac 18F-FDG uptake and magnetic resonance imaging (CMR) was positive identically in the histology-proven and clinically-diagnosed groups. The histology-proven group more frequently had reduce LV ejection fraction, myocardial perfusion abnormality and low-grade electrocardiogram (ECG) abnormality (P=0.003 to 0.016) than did the clinical group. During a 45-month period, the histology-proven group more frequently underwent appropriate implantable cardioverter-defibrillator (ICD) treatment (14% versus 4%, P=0.013) and new electronic device implantation (30% versus 12%, P=0.007) than did clinical group, respectively. There, however, was no difference in all-cause or cardiac mortality or in new hospitalization due to heart failure progression between them. Conclusion: The J-CASP registry demonstrated the rationale and clinical efficacies of non-invasive approach using advanced cardiac imaging modalities in the diagnosis of CS even when histological data were available.

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.

Adverse Cardiac Events in Cardiac Sarcoidosis Prediction by 123I-betamethyl-p-iodophenyl-pentadecanoic Acid Single-Photon Emission Computed Tomography and Cardiac Magnetic Resonance Late Gadolinium Enhancement.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging can help detect myocardial damage. 123I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography (BMIPP-SPECT) was developed to evaluate fatty acid metabolism and has been reported to help detect myocardial damage in cardiac sarcoidosis (CS). We analyzed data from CMR-LGE and performed BMIPP-SPECT in patients with CS taking prednisolone and investigated the association of BMIPP-SPECT with LGE as a prognostic factor in CS. Patients with CS who underwent BMIPP-SPECT and CMR-LGE at the time of diagnosis within 2 months were classified into those with and without a major adverse cardiac event (MACE). Total BMIPP-SPECT defect score (BDS) and LGE extent score (LES) were used to estimate myocardial damage. The relation between BDS and LES was explored using Pearson's correlation coefficient. Their ability to predict MACEs was analyzed using Kaplan-Meier analysis. Medical data of 45 patients were analyzed retrospectively (mean follow-up, 4.5 years). BDS and LES were significantly correlated (p <0.0001). BDS was significantly greater for the group with MACE than that without MACE (p = 0.0008). LES of patients with MACE was significantly greater than those without MACE (p = 0.0045). Patients with BDS ≥16 had a significantly higher MACE rate than those with BDS <16 (p = 0.0029). The group with LES ≥9 was significantly associated with MACE (p = 0.0098). In conclusion, BDS reflected myocardial damage similar to that detected by CMR-LGE and was a predictive marker of MACE in patients with CS. BMIPP-SPECT may help predict the prognosis of patients with CS who cannot undergo CMR-LGE.

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.

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.

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.

Coronary flow quantification estimated by dynamic 320-detector CT angiography: validation by 13N ammonia PET myocardial flow reserve.

OBJECTIVES: Resting coronary flow index (rCFI) estimated by 320-detector low-dose dynamic coronary CT angiography (CCTA) is a direct flow quantification using intracoronary attenuation. We propose modified-rCFI from new protocol combining dynamic scan and standard CCTA using dose-modulation, and validate its consistency with quantitative values and ischemia depicted by 13N-ammonia PET (NH3-PET). METHODS: 46 patients who underwent dynamic CCTA and NH3-PET for coronary artery disease were evaluated using original rCFI in 21 patients and modified-rCFI in 25 patients. Two types of rCFI were calculated for three major coronary arteries. Myocardial blood flow (MBF) at rest and stress, myocardial flow reserve (MFR), and the presence or absence of ischemia for three major territories were depicted by NH3-PET. Coronary territories were categorized as territories with MFR <2.0, ≥2.0, or with and without ischemia. Receiver operating characteristic analysis was performed to determine the optimal cut-off of rCFI to distinguish territories with MFR <2.0 or the presence of ischemia. RESULTS: rCFI and modified-rCFI had significant positive correlations with stress MBF and MFR. The optical cut-offs of rCFI and modified-rCFI of 0.39 and 0.61 could detect territories with MFR <2.0, with AUCs of 0.75 and 0.73, sensitivities of 48 and 34%, and specificities of 97 and 98%. Optimal cut-offs of rCFI and modified-rCFI distinguished ischemic segments from non-ischemic segments, with AUCs of 0.75 and 0.91, sensitivities of 53 and 50%, and specificities of 93 and 95%. CONCLUSION: Two types of rCFI correlated with quantitative values from NH3-PET, and were consistent with a high specificity in detecting functional ischemia. ADVANCES IN KNOWLEDGE: rCFI can contribute as additional functional test over standard CCTA in clinical work-up.

Risk stratification in coronary artery disease using NH3-PET myocardial flow reserve and CAD-RADS on coronary CT angiography.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (NH3-PET) can predict the prognosis of patients with various heart diseases. Coronary computed tomography angiography (CCTA) is a non-invasive investigation for ischemic heart disease. The coronary artery disease reporting and data system (CAD-RADS) was established to standardize and facilitate the reporting of CCTA data regarding CAD. This study aimed to investigate the prognostic value of CAD-RADS and MFR. A total of 133 patients who underwent NH3-PET and CCTA within 3 months were enrolled. Patients were divided into groups with CAD-RADS 0-2 and ≥ 3 and into groups with MFR ≥ 2.0 and < 2.0. The endpoint was major adverse cardiac events (MACE) comprising all-cause death, acute coronary syndrome, hospitalization due to heart failure, and cerebrovascular disease. The ability of CAD-RADS and MFR to predict MACE was analyzed using Kaplan-Meier analysis. There was no significant difference in MFR between patients with CAD-RADS 0-2 and ≥ 3 (2.3 ± 0.9 vs. 2.2 ± 0.7, p = 0.50). The MACE rate for patients with CAD-RADS 0-2 and ≥ 3 was equivalent (log-rank test, p = 0.64). Patients with MFR < 2.0 had a significantly higher MACE rate than those with MFR ≥ 2.0 (p = 0.017). In patients with CAD-RADS ≥ 3, patients with MFR < 2.0 had a significantly higher MACE rate than those with MFR ≥ 2.0 (p = 0.034). CAD-RADS did not contribute to MACE prediction. Conversely, MFR was useful in predicting MACE, allowing for further risk stratification in addition to CAD-RADS.

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.

Association of coronary revascularisation after physician-referred non-invasive diagnostic imaging tests with outcomes in patients with suspected coronary artery disease: a post hoc subgroup analysis.

OBJECTIVE: We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease. DESIGN: A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study. SETTING: Multiple centres in Japan. PARTICIPANTS: From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ2 test, Student's t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis. RESULTS: A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p<0.0001; CT stratum: 6.1 vs 0.8%, log-rank p=0.0001), there was no interaction between the risk of revascularisation and the imaging strata (SPECT stratum: adjusted HR (95% CI), 4.25 (1.86-9.72); CT stratum: 4.13 (1.16-14.73); interaction: p=0.97). CONCLUSION: The association of revascularisation with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion.

Impact of renal dysfunction on the choice of diagnostic imaging, treatment strategy, and outcomes in patients with stable angina.

We investigated the interaction between the prognostic impact of a decrease in eGFR and the choice of initial diagnostic imaging modality for coronary artery disease. Out of 2878 patients who enrolled in the J-COMPASS study, 2780 patients underwent single photon emission computed tomography (SPECT), coronary computed tomography (CT) angiography, or coronary angiography (CAG) as an initial diagnostic test. After excluding patients with routine hemodialysis or lacked serum creatinine levels, 2096 patients in the non-decreased eGFR group (eGFR ≥ 60 ml/min/1.73 m2) and 557 patients in the decreased eGFR group (eGFR < 60 ml/min/1.73 m2) were analyzed in this study. Major adverse cardiac events, including death, myocardial infarction, heart failure hospitalization, and late revascularization, were followed, with a median follow-up duration of 472 days. SPECT or CAG was preferable to CT in patients in the decreased eGFR group (p < 0.0001 and p = 0.0024, respectively). There was a marginally significant interaction between the prognostic impact of a decrease in eGFR and the choice of diagnostic imaging modality (interaction-p = 0.056). A decrease in eGFR was not associated with a poor outcome in patients who underwent CT, while a decrease in eGFR was associated with poor outcomes in patients who underwent SPECT or CAG. In conclusion, the prognostic impact of a decrease in eGFR tended to be different among the initial imaging modalities.

Discrepancy between significant fibrosis and active inflammation in patients with cardiac sarcoidosis: combined and image fusion analysis of cardiac magnetic resonance and 18F fluorodeoxyglucose positron emission tomography.

BACKGROUND: Diagnosis and evaluation of cardiac sarcoidosis (CS) are mainly based on the combined use of cardiac magnetic resonance imaging (CMR) and 18F fludeoxyglucose positron emission tomography (FDG). Though these modalities can detect the pathological feature of the disease, combined assessment has not been fully examined. Multimodality image fusion is known to be useful for further comprehension, while most image interpretation is performed with a side by side comparison in clinical routine. We investigated the similarity and discrepancy of active inflammation, regional fibrosis, and wall function by image fusion of CMR and FDG. METHODS: Patients with CS who underwent both CMR and FDG were retrospectively enrolled. The extent of myocardial late gadolinium enhancement (LGE) in left ventricle (LGE volume), cardiac function, and volume (left ventricular ejection fraction, LVEF; end-diastolic volume, EDV) was measured from CMR. The FDG uptake in whole myocardium (whole SUVmax), cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) was calculated from FDG. CMR and FDG were fused and divided into AHA 17 model for segmental analysis. Wall motion, the magnitude of LGE in myocardial wall (LGE%wall), and corresponding FDG uptake (segmental SUVmax) were analyzed. RESULTS: Forty-one patients were retrospectively enrolled. In patients with FDG uptake, LVEF inversely correlated to LGE volume and positively correlated to SUVmax (r = - 0.56, p < 0.0001, and r = 0.08, p = 0.048, respectively). Discrepancy between LGE volume and CMV showed a significant positive correlation to whole SUVmax and CMA (r = 0.49, p < 0.0001, and r = 0.96, p < 0.0001, respectively). In image fusion analysis, segmental SUVmax showed a significant inverse correlation to LGE%wall (Spearman's rank correlation coefficient; r = - 0.15, p = 0.008). LGE%wall also showed significant inverse correlation to wall motion (r = - 0.13, p = 0.0011). CONCLUSION: Combined and fusion analysis with CMR and FDG demonstrated the discrepancy of myocardial inflammation and extensive fibrosis. Active inflammation was present in the earlier stage of myocardial fibrosis and was found to be less in the wall with advanced fibrosis and remodeling. Combined analysis of CMR and FDG can incrementally reclassify the pathological stage of CS.

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.