Improvement of motion artifacts using dynamic whole-body 18F-FDG PET/CT imaging.

PURPOSE: Serial dynamic whole-body PET imaging is valuable for assessing serial changes in tracer uptake. The purpose of this study was to evaluate the improvement of motion artifacts in patients using serial dynamic whole-body 18F-fluorodeoxyglyucose (FDG) PET/CT imaging. MATERIALS AND METHODS: In 797 consecutive patients, serial 3-min dynamic whole-body FDG PET imaging was performed seven times, at 60 or 90 min after FDG administration. In cases with large body motion during imaging, we tried to improve the images by summing the images before body motion. An image quality study was performed on another 50 patients without obvious body motion using the same acquisition mode. RESULTS: Obvious body movement was observed in 106 of 797 cases (13.3%), and severe motion artifacts which interfered image interpretation were observed in 18 (2.3%). In these 18 cases, summation of the images before the body movement enabled us to obtain images that excluded the effect of the body motion. In the visual evaluation of the image quality in another 50 patients studied, acceptable image quality was obtained when 2 or more times the serial 3-min image data were added. CONCLUSION: Serial dynamic whole-body FDG PET imaging can minimize body motion artifacts by summation of the images before the body motion. Such serial dynamic study may be a choice for PET imaging to eliminate motion artifacts.

Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure.

Aims: Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined. Methods: A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs). Results: The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m2 and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables. Conclusion: Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.

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.

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.

Prediction of multivessel coronary artery disease and candidates for stress-only imaging using multivariable models with myocardial perfusion imaging.

PURPOSE: Selecting patients with coronary multivessel disease (MVD) or no stenosis using myocardial perfusion imaging (MPI) is challenging. We aimed to create a model to predict MVD using a combination of quantitative MPI values and background factors of patients. We also assessed whether patients in the same database could be selected who do not require rest studies (stress-only imaging). METHODS: We analyzed data from 1001 patients who had been assessed by stress MPI at 12 centers and 463 patients who had not undergone revascularization in Japan. Quantitative values based on MPI were obtained using cardioREPO software, which included myocardial perfusion defect scores, left ventricular ejection fractions and volumes. Factors in MPI and clinical backgrounds that could predict MVD were investigated using univariate and multivariate analyses. We also investigated whether stress data alone could predict patients without coronary stenosis to identify candidates for stress-only imaging. RESULTS: We selected summed stress score (SSS), rest end-diastolic volume, and hypertension to create a predictive model for MVD. A logistic regression model was created with an area under the receiver operating characteristics curve (AUC) of 0.825. To more specifically predict coronary three-vessel disease, the AUC was 0.847 when SSS, diabetes, and hypertension were selected. The mean probabilities of abnormality based on the MVD prediction model were 12%, 24%, 40%, and 51% for no-, one-, two-, and three-vessel disease, respectively (p < 0.0001). For the model to select patients with stress-only imaging, the AUC was 0.78 when the model was created using SSS, stress end-systolic volume and the number of risk factors (diabetes, hypertension, chronic kidney disease, and a history of smoking). CONCLUSION: A model analysis combining myocardial SPECT and clinical data can predict MVD, and can select patients for stress-only tests. Our models should prove useful for clinical applications.

Prognostic value of nutritional parameters in systolic heart failure with renal dysfunction.

Although it is known that assessment and management of the nutritional status of patients are important for treatment of patients with heart failure (HF), there are currently no established indicators. Therefore, we investigated the effects of nutritional parameters as well as conventional parameters on the prognosis of HF patients. A total of 1954 consecutive HF patients with left ventricular ejection fraction (LVEF) less than 50% were enrolled in this study. Transthoracic echocardiography was performed and conventional parameters for HF patients and parameters to assess nutritional status were measured in all patients. Patients were followed up with a primary endpoint of lethal cardiac events (CEs) for 30.2 months. During the follow-up period, cardiac events were documented in 619 HF patients. The CEs group had a lower level of cholinesterase (201.5U/L vs 265.2U/L, P <0.0001), lower estimated GFR (35.2 ml/min/1.73m2 vs 50.3ml/min/1.73m2, P< 0.0001), and lower Geriatric Nutritional Risk Index (GNRI) (91.9 vs 100.0, P< 0.0001) than those in the non-CEs group. Serum cholinesterase, estimated GFR, and GNRI were identified as significant prognostic determinants in multivariate analysis. ROC analyses revealed cut-off values of serum cholinesterase, estimated GFR, and GNRI of 229U/L, 34.2 ml/min/1.73m2, and 95.6, respectively, for identifying high-risk HF patients. HF patients with serum cholinesterase< 229U/L, estimated GFR<34.3 ml/min/1.73m2, and GNRI< 95.6 had a significantly greater rate of CEs than that in the other patients (P<0.0001). Low serum cholinesterase and low GNRI can predict cardiac mortality risk in systolic HF patients with renal dysfunction.

Machine learning-based risk model using 123I-metaiodobenzylguanidine to differentially predict modes of cardiac death in heart failure.

BACKGROUND: Cardiac sympathetic dysfunction is closely associated with cardiac mortality in patients with chronic heart failure (CHF). We analyzed the ability of machine learning incorporating 123I-metaiodobenzylguanidine (MIBG) to differentially predict risk of life-threatening arrhythmic events (ArE) and heart failure death (HFD). METHODS AND RESULTS: A model was created based on patients with documented 2-year outcomes of CHF (n = 526; age, 66 ± 14 years). Classifiers were trained using 13 variables including age, gender, NYHA functional class, left ventricular ejection fraction and planar 123I-MIBG heart-to-mediastinum ratio (HMR). ArE comprised arrhythmic death and appropriate therapy with an implantable cardioverter defibrillator. The probability of ArE and HFD at 2 years was separately calculated based on appropriate classifiers. The probability of HFD significantly increased as HMR decreased when any variables were combined. However, the probability of arrhythmic events was maximal when HMR was intermediate (1.5-2.0 for patients with NYHA class III). Actual rates of ArE were 3% (10/379) and 18% (27/147) in patients at low- (≤ 11%) and high- (> 11%) risk of developing ArE (P < .0001), respectively, whereas those of HFD were 2% (6/328) and 49% (98/198) in patients at low-(≤ 15%) and high-(> 15%) risk of HFD (P < .0001). CONCLUSION: A risk model based on machine learning using clinical variables and 123I-MIBG differentially predicted ArE and HFD as causes of cardiac death.

Health economics-based verification of functional myocardial ischemia evaluation of stable coronary artery disease in Japan: A long-term longitudinal study using propensity score matching.

BACKGROUND: The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD). METHODS AND RESULTS: We reviewed patients' medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043). CONCLUSIONS: The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.

Improved risk-stratification in heart failure patients with mid-range to severe abnormalities of QRS duration and systolic function using mechanical dyssynchrony assessed by myocardial perfusion-gated SPECT.

BACKGROUND: The use of left ventricular mechanical dyssynchrony (LVMD), which has been reported to be responsible for unfavorable outcomes, might improve conventional risk-stratification by clinical indices including QRS duration (QRSd) and systolic dysfunction in patients with heart failure (HF). METHODS AND RESULTS: Following measurements of 12-lead QRSd and left ventricular ejection fraction (LVEF), three-dimensional (3-D) LVMD was evaluated as a standard deviation (phase SD) of regional mechanical systolic phase angles by gated myocardial perfusion imaging in 829 HF patients. Patients were followed up for a mean period of 37 months with a primary endpoint of lethal cardiac events (CEs). In an overall multivariate Cox proportional hazards model, phase SDs were identified as significant prognostic determinants independently. The patients were divided into 4 groups by combining with the cut-off values of LVEF (35% and 50%) and QRSd (130 ms and 150 ms). The groups with lower LVEF and prolonged QRSd more frequently had CEs than did the other groups. Patient groups with LVEF < 35% and with 35% ≦ LVEF < 50% were differentiated into low-risk and high-risk categories by using an optimal phase SD cut-off value of both QRSd thresholds. CONCLUSIONS: 3-D LVMD can risk-stratify HF patients with mid-range as well as severe abnormalities of QRSd and systolic dysfunction.

Impaired Cardiac Sympathetic Innervation Increases the Risk of Cardiac Events in Heart Failure Patients with Left Ventricular Hypertrophy and Mechanical Dyssynchrony.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD), left ventricular hypertrophy, and impaired cardiac sympathetic innervation are closely related to the development of heart failure (HF) and unfavorable outcomes. METHODS AND RESULTS: A total of 705 consecutive HF patients with reduced left ventricular ejection fraction (EF) < 50% were registered in our hospital HF database. LVMD and left ventricular mass index (LVMI) were evaluated three-dimensionally by gated myocardial perfusion SPECT. LVMD was measured as a heterogeneity index (phase SD) of the regional contraction phase angles calculated by Fourier analysis. Cardiac sympathetic innervation was quantified as a normalized heart-to-mediastinum ratio (HMR) of the 123I-metaiodobenzylguanidine (MIBG) activity. The patients were followed up with a primary end point of lethal cardiac events (CEs) for 42 months. CEs were documented in 246 of the HF patients who had a greater phase SD, greater LVMI, and lower MIBG HMR than those in HF patients without CEs. In the overall multivariate analysis, phase SD, LVMI, and MIBG HMR were identified as significant CE determinants. The three biomarkers were incrementally related to increases in CE risks. CONCLUSIONS: Assessment of cardiac sympathetic innervation can further stratify patients with systolic heart failure at increased cardiac risk identified by left ventricular hypertrophy and mechanical dyssynchrony.

A novel approach to the selection of an appropriate pacing position for optimal cardiac resynchronization therapy using CT coronary venography and myocardial perfusion imaging: FIVE STaR method (fusion image using CT coronary venography and perfusion SPECT applied for cardiac resynchronization therapy).

BACKGROUND: Nearly one-third of patients with advanced heart failure (HF) do not benefit from cardiac resynchronization therapy (CRT). We developed a novel approach for optimizing CRT via a simultaneous assessment of the myocardial viability and an appropriate lead position using a fusion technique with CT coronary venography and myocardial perfusion imaging. METHODS AND RESULTS: The myocardial viability and coronary venous anatomy were evaluated by resting Tc-99m-tetrofosmin myocardial perfusion imaging (MPI) and contrast CT venography, respectively. Using fusion images reconstructed by MPI and CT coronary venography, the pacing site and lead length were determined for appropriate CRT device implantations in 4 HF patients. The efficacy of this method was estimated by the symptomatic and echocardiographic functional parameters. In all patients, fusion images using MPI and CT coronary venograms were successfully reconstructed without any misregistration and contributed to an effective CRT. Before the surgery, this method enabled the operators to precisely identify the optimal indwelling site, which exhibited myocardial viability and had a lead length necessary for an appropriate device implantation. CONCLUSIONS: The fusion image technique using myocardial perfusion imaging and CT coronary venography is clinically feasible and promising for CRT optimization and enhancing the patient safety in patients with advanced HF.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Translation, adaptation and validation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) for use in Japan: a multicentre cross-sectional study.

OBJECTIVES: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) is a well-established and internationally recognised scale for measuring patients' experience with hospital inpatient care. This study aimed to develop a Japanese version of the HCAHPS and to examine its structural validity, criterion-related validity and internal consistency reliability. DESIGN: Multicentere cross-sectional study. SETTING: A total of 48 hospitals in Japan. PARTICIPANTS: 6522 patients aged ≥16 years who were discharged from the participating hospitals. RESULTS: Confirmatory factor analysis showed excellent goodness of fit of the same factor structure as that of the original HCAHPS, with the following composites: communication with nurses, communication with doctors, responsiveness of hospital staff, hospital environment, communication about medicines and discharge information. All hospital-level Pearson correlation coefficients between the Japanese HCAHPS composites and overall hospital rating exceeded the criteria. Results of inter-item correlations indicated adequate internal consistency reliability. CONCLUSIONS: The Japanese HCAHPS has acceptable psychometric properties for assessing patients' experience with hospital inpatient care. This scale could be used for quality improvement based on the assessment of patients' experience with hospital care and for health services research in Japan.

Dynamic Whole-Body 18F-FDG PET for Minimizing Patient Motion Artifact.

Recent PET/CT systems permit short acquisition with acceptable image quality. In addition, continuous-bed-motion mode is available for whole-body PET imaging with some PET cameras providing better uniformity and reproducibility throughout the field of view. We demonstrate a case with patient motion during the dynamic scan. Although the total summation of serial whole-body scan showed image artifact, the first 15 minutes' summation of the serial scans provided high-quality images by eliminating the frames with motion. This acquisition mode seems to be particularly useful to perform for those who may likely to move during PET scan.

Synergistic prognostication of left ventricular hypertrophy and three-dimensional mechanical dyssynchrony in heart failure.

AIMS: In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three-dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: In 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time-activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non-CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non-CE group. Phase SD > 37 and LVMI > 122.7 g/m2 were identified as optimal cut-off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut-off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m2 had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024-1.051, P < 0.0001) and 1.005 (CI, 1.001-1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ2 value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI. CONCLUSIONS: Three-dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.

Paradoxical Prognostic Implications of Visceral Adiposity for Lethal Cardiac Events in Association with Impaired Cardiac Sympathetic Innervation in Chronic Heart Failure.

Background: Obesity increases the risk for development of heart failure (HF) but, when present is likely to be related to better outcomes in patients with HF. This study aimed to clarify the paradoxical prognostic values of visceral obesity in association with cardiac sympathetic function in HF patients. Methods and Results: A total of 653 consecutive patients with systolic HF who underwent visceral adiposity area (VAA) measurements using a computed tomographic technique were divided into 3 groups: VAA 1, area <80 cm2; VAA 2, area 80-140 cm2; VAA 3, area >140 cm2. Sympathetic innervation was quantified by 123I-MIBG cardiac activity. Patients were followed up for an average of 22 months with a primary endpoint of lethal cardiac events (CE). The CE group (n=200) had a lower late heart-to mediastinum ratio (HMR) and a smaller VAA than those in the non-CE group. Rates of overall CE/HF death were inversely correlated with VAA: 39.2% ± 6.2% for VAA 1, 27.4% ± 19.9% for VAA 2 and 24.1% ± 15.3% for VAA 3. In addition to sudden cardiac death rate, lethal arrhythmic event rate increased in association with visceral fat obesity: 3.0% for VAA 1, 7.5% for VAA 2 and 8.8% for VAA 3. Late HMR identified high-risk sub-populations in each group. Conclusion: Visceral obesity has paradoxical prognostic implications in terms of HF mortality and lethal arrhythmic/sudden cardiac death events. Cardiac sympathetic denervation and quantitative visceral adiposity are synergistically associated with overall cardiac mortality, contributing to better risk stratification of HF patients.

Design of the Japanese Comprehensive Health-Economic Assessment for Appropriate Cardiac Imaging Strategy Including Outcome and Cost-Effectiveness in Stable Coronary Artery Disease Study (J-CONCIOUS).

Background: The evaluation of stable coronary artery disease (SCAD) has evolved, and contemporary clinical practice guidelines emphasize the importance of in-depth consideration of procedure indications, risk stratification, and results of non-invasive imaging tests. However, little is known about the appropriate selection of imaging modalities for ischemia evaluation and the comparative cost-effectiveness in real-world clinical practice. Methods and Results: The Japanese Comprehensive Health-Economic Assessment for Appropriate Cardiac Imaging Strategy including Outcome and cost-effectiveness in Stable Coronary Artery Disease Study (J-CONCIOUS), a multicenter observational study, was designed to prospectively enroll 2,500 patients with suspected or known SCAD, register clinical information and administrative records, and follow patients for 3 years. Any diagnostic or cardiac imaging modality (including stress tests using electrocardiography, echocardiography, or myocardial perfusion imaging; coronary computed tomographic angiography; and/or invasive coronary angiography with or without fractional flow reserve assessment) is acceptable. Clinical endpoints, such as all-cause mortality, cardiac death, and non-fatal myocardial infarction, will be obtained, along with quality of life assessment using the Seattle Angina Questionnaire. The cost-effectiveness of individual assessment patterns will be quantified by analysis of Diagnosis Procedure Combination (DPC) data, and quality-adjusted life years and the incremental cost-effectiveness ratio will be calculated. Conclusions: J-CONCIOUS is expected to establish a risk-based and cost-effective imaging strategy for the detection and evaluation of functional myocardial ischemia and/or anatomical coronary imaging in Japan.

Validation of 2-year 123I-meta-iodobenzylguanidine-based cardiac mortality risk model in chronic heart failure.

Aims: The aim of this study was to validate a four-parameter risk model including 123I-meta-iodobenzylguanidine (MIBG) imaging, which was previously developed for predicting cardiac mortality, in a new cohort of patients with chronic heart failure (CHF). Methods and results: Clinical and outcome data were retrospectively obtained from 546 patients (age 66 ± 14 years) who had undergone 123I-MIBG imaging with a heart-to-mediastinum ratio (HMR). The mean follow-up time was 30 ± 20 months, and the endpoint was cardiac death. The mortality outcome predicted by the model was compared with actual 2-year event rates in pre-specified risk categories of three or four risk groups using Kaplan-Meier survival analysis for cardiac death and receiver-operating characteristic (ROC) analysis. Cardiac death occurred in 137 patients, including 105 (68%) patients due to heart-failure death. With a 2-year mortality risk from the model divided into three categories of low- (<4%), intermediate- (4-12%), and high-risk (>12%), 2-year cardiac mortality was 1.1%, 7.9%, and 54.7%, respectively in the validation population (P < 0.0001). In a quartile analysis, although the predicted numbers of cardiac death was comparable with actual number of cardiac death for low- to intermediate-risk groups with a mortality risk <13.8%, it was underestimated in the high-risk group with a mortality risk ≥13.8%. The ROC analysis showed that the 2-year risk model had better (P < 0.0001) diagnostic ability for predicting heart failure death than left ventricular ejection fraction, natriuretic peptides or HMR alone. Conclusion: The 2-year risk model was successfully validated particularly in CHF patients at a low to intermediate cardiac mortality risk.

Synergistic prognostic implications of left ventricular mechanical dyssynchrony and impaired cardiac sympathetic nerve activity in heart failure patients with reduced left ventricular ejection fraction.

Aims: Impairment of cardiac sympathetic innervation is a potent prognostic marker in heart failure, while left ventricular mechanical dyssynchrony (LVMD) has recently been noted as a novel prognosis determinant in heart failure patients with reduced LV ejection fraction (HFrEF). This study was designed to determine the correlation between cardiac sympathetic innervation quantified by metaiodobenzylguanidine (MIBG) activity and LVMD measured by electrocardiogram-gated myocardial perfusion imaging and to evaluate their incremental prognostic values in HFrEF patients. Methods and results: A total of 570 consecutive HFrEF patients were followed up for 19.6 months with a primary endpoint of lethal cardiac events (CE) such as sudden cardiac death, death due to pump failure and appropriate ICD shock against life-threatening ventricular tachyarrhythmias. Cardiac sympathetic function and innervation were quantified as heart-to-mediastinum ratio (HMR) and washout kinetics of cardiac MIBG activity. LVMD was assessed by a standard deviation (SD) of systolic phase angle in gated myocardial perfusion imaging. Patients with CE (n = 166, 29%) had a significantly lower HMR and a significantly greater phase SD than did non-CE patients: 1.46 ± 0.28 vs. 1.63 ± 0.29, P < 0.0001 and 39.1 ± 11.6 vs. 33.1 ± 10.1, P < 0.0001, respectively. Compared to the single use of optimal cut-offs of late HMR (1.54) and phase SD (38), their combination more precisely discriminated high-risk or low-risk patients from others with log rank values from 7.78 to 65.2 (P = 0.0053 to P ≤ 0.0001). Among significant univariate variables, multivariate Cox proportional hazards model identified NYHA functional class, estimated glomerular filtration rate (eGFR), HMR 1.54 and phase SD 60 as significant determinants of CE with hazard ratios of 3.108 (95% CI, 2.472-3.910; P < 0.0001), 0.988 (95% CI, 0.981-0.996; P = 0.0021), 0.257 (95% CI, 0.128-0.498; P < 0.0001) and 1.019 (95% CI, 1.019-1.037; P = 0.0228), respectively. By combining the four independent determinants, the prognostic powers synergistically (P < 0.0001) increased maximally to 263.8. Conclusions: Left ventricular mechanical dyssynchrony and impairment of cardiac sympathetic innervation are synergistically related to lethal cardiac events, contributing to better stratification of lethal cardiac event-risks and probably to optimization of therapeutic strategy in patients with HFrEF.