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.

Prognostic impact of reducing myocardial ischemia identified using ECG-gated myocardial perfusion SPECT in Japanese patients with coronary artery disease: J-ACCESS 4 study.

AIM: Whether myocardial ischemia identified using myocardial perfusion imaging (MPI) can be an alternative target of coronary revascularization to reduce the incidence of cardiac events remains unclear. METHODS AND RESULTS: This multicenter, prospective cohort study aimed to clarify the prognostic impact of reducing myocardial ischemia. Among 494 registered patients with possible or definite coronary artery disease (CAD), 298 underwent initial pharmacological stress 99mTc-tetrofosmin MPI before, and eight months after revascularization or medical therapy, and were followed up for at least one year. Among these, 114 with at least 5% ischemia at initial MPI were investigated. The primary endpoints were cardiac death, non-fatal myocardial infarction and hospitalization for heart failure. Ischemia was reduced ≥5% in 92 patients. Coronary revascularization reduced ischemia (n = 89) more effectively than medical therapy (n = 25). Post-stress cardiac function also improved after coronary revascularization. Ejection fraction significantly improved at stress (61.0% ±â€¯10.7% vs. 65.4% ±â€¯11.3%; p < 0.001) but not at rest (67.1% ±â€¯11.3% vs. 68.3% ±â€¯11.6%; p = 0.144), among patients who underwent revascularization. Rates of coronary revascularization and cardiac events among the 114 patients were significantly higher (13.6%, p = 0.035) and lower (1.1% p = 0.0053), respectively, in patients with, than without ≥5% ischemia reduction. Moreover, patients with complete resolution of ischemia at the time of the second MPI had a significantly better prognosis. CONCLUSIONS: Reducing ischemia by ≥5% and the complete resolution of ischemia could improve the prognosis of patients with stable CAD.

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.

Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database.

As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of (123)I-MIBG sympathetic imaging was performed regarding heart-to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches.

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.

Prognostic study of cardiac and renal events in Japanese patients with chronic kidney disease and cardiovascular risk using myocardial perfusion SPECT: J-ACCESS 3 study design.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease. Recent studies have indicated that the incidence of cardiovascular disease increases inversely with estimated glomerular filtration rate. Although coronary angiography is considered the gold standard for detecting coronary artery disease, contrast-induced nephropathy or cholesterol microembolization remain serious problems; therefore, a method of detecting coronary artery disease without renal deterioration is desirable. From this viewpoint, stress myocardial perfusion single photon emission computed tomography (SPECT) might be useful for patients with chronic kidney disease. We recently performed the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) investigating patients with suspected or extant coronary artery disease and the J-ACCESS 2 study of patients with diabetes. The findings from these studies showed that SPECT can detect coronary artery disease and help to predict future cardiac events. Thus, we proposed a multicenter, prospective cohort study called "J-ACCESS 3" in patients with chronic kidney disease and cardiovascular risk. The study aimed at predicting cardiovascular and renal events based on myocardial perfusion imaging and clinical backgrounds. We began enrolling patients in J-ACCESS 3 at 74 facilities from April 2009 and will continue to do so until 31 March 2010, with the aim of having a cohort of 800 patients. These will be followed up for three years. The primary endpoints will be cardiac death and sudden death. The secondary endpoints will comprise any cardiovascular or renal events. This study will be completed in 2013. Here, we describe the design of the J-ACCESS 3 study.

Clinical significance of B-type natriuretic Peptide in the assessment of untreated hypertension.

BACKGROUND: Recent studies suggest that B-type natriuretic peptide (BNP) is an important predictor of cardiac events in hypertensive patients. METHODS AND RESULTS: The relationship between the plasma BNP level and various clinical parameters was examined in 154 untreated hypertensive patients without heart failure or atrial fibrillation (mean age: 58.0+/-10.7; mean blood pressure: 164.5+/-15.2/99.1+/-9.7 mmHg; mean BNP: 32.7+/-36.7 pg/ml). First, the patients were divided into 2 groups based on BNP: normal (<18.5 pg/ml, mean 9.7+/-5.7, n=69); or elevated (>18.5 pg/ml, mean 51.4+/-40.4, n=85). The elevated BNP group had a significantly greater electrocardiographic voltage index (SV1+RV5; 3.7+/-1.2 vs 3.2+/-0.8 mV, p=0.0029), cardiothoracic ratio/chest radiography (CTR; 49.1 vs 46.9%, p=0.0037), left ventricular mass index (LVMI; 122.2+/-31.7 vs 103.1+/-26.4 g/m2, p=0.0005) and deceleration time (DT; 241+/-39 vs 208+/-30 ms, p=0.0001), as well as a smaller E-wave to A-wave (E/A ratio) (0.80+/-0.22 vs 0.96+/-0.28, p=0.0003), compared with the normal BNP group. There were no significant differences in casual blood pressure, body mass index, serum creatinine and ejection fraction between the 2 groups. Next, the patients were divided into 3 groups based on BNP: normal (<18.5, n=69), moderate (18.5 to 40, mean 27.0+/-5.7, n=43) and high (40<, mean 76.3+/-45.3, n=42). In the high BNP group, most clinical parameters indicated the most severe organ damage compared with other groups, including SV1+RV5, DT and LVMI. In all patients, logarithmic BNP was positively correlated with the age, pulse pressure, SV1+RV5, CTR, ventricular wall thickness, DT, LVMI and negatively correlated with hemoglobin, renin and E/A ratio. Using multiple regression analysis, renin and DT were significantly associated with BNP. No gender differences in the relationship between BNP and clinical parameters were found. CONCLUSIONS: Results suggest that BNP is a useful indicator for the initial assessment of the severity of essential hypertension, detecting both cardiac hypertrophy and diastolic dysfunction, and may also be valuable for risk stratification.

Pericarditis causing congestive heart failure as an initial manifestation of systemic lupus erythematosus.

Pericarditis is a common complication in systemic lupus erythematosus (SLE) patients, however, that causing congestive heart failure (CHF) is a rare initial manifestation of SLE. We treated a patient whose initial manifestation of SLE was pericardial effusion causing CHF, which improved following prednisolone therapy that led to a dramatic decrease in pericardial effusion and improvement in left ventricular diastolic dysfunction as shown in Doppler echocardiography findings. Further, the plasma brain natriuretic peptide level became normalized.

"W-shaped" volume curve with gated myocardial perfusion single photon emission computed tomography.

OBJECTIVES: Gating errors (GEs) with ECG gated myocardial SPECT (G-SPECT) may occur irrespective of the presence or absence of arrhythmias. We evaluated the impact of GEs on both reconstructed tomograms and left ventricular ejection fraction (LVEF) derived from G-SPECT, and searched for clues to identify these errors. METHODS: We studied 2 GE patients, 10 normal subjects (NLs), and 10 atrial fibrillation patients. Stress technetium-99m sestamibi G-SPECT was performed. Left ventricular (LV) contraction was evaluated in the beating slices. LVEF was calculated with G-SPECT using QGS (Cedars-Sinai, Los Angels) and p-FAST (Sapporo Medical University, Japan), and compared with that obtained by echocardiography (ECHO). LV volume curves were created by QGS and p-FAST. The heart rates (HRs) were calculated from the acquired images, and compared with their resting HRs. The mean count density of the myocardium was measured and time-activity curves were created. RESULTS: In patients with GEs, bi-phasic LV contraction was demonstrated with fading-out towards end-diastole. G-SPECT underestimated LVEF compared to ECHO by 10% or more. The volume curves appeared "W-shaped." The HRs from the images were slower than the resting HRs. The count density decrement from frame #1 to #8 was larger than that of NLs. The time-activity curves were different in shape from those of NLs. CONCLUSIONS: G-SPECT underestimates LVEF in patients with GEs. These errors can be identified with a combination of visual inspection of beating slices, time-volume curves, and time-activity curves. Monitoring the HR is a clue for anticipating and avoiding these errors.

Compared with 3-dimensional analysis, 2-dimensional gated SPECT analysis overestimates left ventricular ejection fraction in patients with regional dyssynchrony.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) is a powerful prognostic predictor in patients with heart disease. However, LVEF calculated by 2-dimensional (2D) modalities such as echocardiography by use of the "modified" Simpson's rule may be incorrect in patients with regional dyssynchrony, presumably because regions of dyssynchrony are excluded from analysis. METHODS AND RESULTS: To elucidate the difference between 2D and 3-dimensional (3D) methods with regard to LVEF calculation in patients with regional dyssynchrony, we compared LVEF derived from 8-frame gated technetium 99m sestamibi stress perfusion tomograms using commercially available 2D single photon emission computed tomography (SPECTEF) software that uses the modified Simpson's rule, 3D QGS, and investigational 3D p-FAST software in 136 left bundle branch block patients. Twenty-four patients had normal wall motion, whereas one hundred twelve showed septal dyssynchrony. Bland-Altman plots demonstrated that compared with QGS and p-FAST, SPECTEF overestimated LVEF in patients with septal dyssynchrony systemically by 8.6% and 11.3%, respectively. CONCLUSIONS: We conclude that compared with 3D modalities, 2D modalities that use the modified Simpson's rule, such as SPECT EF, overestimate LVEF in patients with dyssynchronous septal wall motion. Therefore 3D modalities are preferred to evaluate patients with regional dyssynchrony.

F-18 fluorodeoxyglucose uptake in atherosclerotic plaque in the mediastinum mimicking malignancy: another potential for error.

Atherosclerosis is an inflammatory process accumulating numerous inflammatory cells such as macrophages and lymphocytes. This cellular infiltrate has a high metabolic demand, which can be reflected on F-18 FDG positron emission tomographic (PET) imaging. The FDG uptake in atherosclerotic vessels is usually distinguishable as a result of its linear and continuous appearance and mild level of activity. However, occasionally, atherosclerotic plaques present themselves as focal "hot spots," which can be easily misinterpreted as malignancy. This report emphasizes atherosclerotic plaques as a potential pitfall while interpreting FDG scans. It also highlights the importance of radiographic correlation to avoid such an error.

Decreased septal wall thickening in patients with left bundle branch block.

OBJECTIVES: Septal wall motion abnormalities are frequently observed in patients with left bundle branch block (LBBB). However, septal wall thickening in LBBB patients has not been thoroughly evaluated. METHODS AND RESULTS: To investigate the relationship between septal wall motion and wall thickening, we studied 31 normal control subjects, 24 LBBB patients with normal wall motion (LBBB-NWM), and 24 LBBB patients with septal dyssynchrony (LBBB-SDS), all with a low likelihood (<15%) of coronary artery disease. The septal and lateral quadrants of the left ventricle were analyzed in stress 8-frame gated technetium 99m sestamibi tomograms. The percent wall thickening was calculated by use of a 25-segment polar map with the p-FAST software program by two independent methods: the regional count density increase from end diastole to end systole (CD method) and the geometric increase in the distance between the 50% thresholded endocardial and epicardial borders from end diastole to end systole (GD method). In addition, the ratio of septal/lateral percent wall thickening was calculated. The relative septal wall thickening in the entire LBBB population was decreased as compared with the normal control subjects (0.35 +/- 0.37 vs 0.81 +/- 0.17, P <.001). Decreased wall thickening was observed in not only LBBB-SDS patients but also to a lesser degree in LBBB-NWM patients (0.12 +/- 0.35, P <.001; 0.57 +/- 0.24, P =.005, respectively). This abnormality was most apparent when the CD method was used. CONCLUSIONS: Septal wall thickening is decreased in patients with LBBB even with normal wall motion. LBBB per se may compromise septal wall thickening, and dyssynchronous wall motion results in further deterioration of wall thickening.