J-ACCESS investigation and nuclear cardiology in Japan: implications for heart failure.

While coronary heart disease remains a global cause of mortality, the prevalence of heart failure (HF) is increasing in developed countries including Japan. The continuously increasing aging population and the relatively low incidence of ischemic origins are features of the HF background in Japan. Information about nuclear cardiology practice and prognosis has accumulated, thanks to the multicenter prognostic J-ACCESS investigations (Series 1‒4) over two decades in Japan. Although the rate of hard cardiac events is lower in Japan than in the USA and Europe, similar predictors have been identified as causes of major adverse cardiac events. The highest proportion (50-75%) of major events among patients indicated for nuclear cardiology examinations in the J-ACCESS registries is severe HF requiring hospitalization. Therefore, the background and the possible reasons for the higher proportion of severe HF events in Japan require clarification. Combinations of age, myocardial perfusion defects, left ventricular dysfunction, and comorbid diabetes and chronic kidney disease are major predictors of cardiovascular events including severe HF. Although the Japanese Circulation Society has updated its clinical guidelines to incorporate non-invasive imaging modalities for diagnosing chronic coronary artery disease, the importance of risk-based approaches to optimal medical therapy and coronary revascularization is emphasized herein.

Cardiovascular event risk estimated by myocardial perfusion SPECT combined with clinical data.

Myocardial scintigraphy plays important roles in the diagnosis of coronary artery disease, prognostic risk stratification, and determination of the treatment policy. Recently, several large-scale clinical trials reported that coronary intervention was not necessarily advantageous for preventing future cardiac events in patients with stable angina. This review summarizes how we can estimate cardiac event risks based on Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), and describes that the combination of scintigraphy and other clinical features leads to more accurate stratification of prognosis and the determination of subsequent treatment policy.

Cardiovascular event risk estimated after coronary revascularization and optimal medical therapy: J-ACCESS4 prognostic study.

BACKGROUND: An assessment of cardiac events and survival using quantitative gated myocardial single-photon emission computed tomography (SPECT) (J-ACCESS) associated several risk factors with cardiac events in Japan. The clinical course after revascularization and/or optimal medical therapy (OMT) was followed in patients with coronary artery disease (CAD) at moderate-to-high risk estimated by software incorporating the J-ACCESS risk model. The present study aimed to determine the relevance of changes in estimated risk to outcomes of these therapies. METHODS: This study included 494 patients with possible or definite CAD who underwent initial pharmacological stress 99mTc-tetrofosmin myocardial perfusion SPECT (MPS) before and eight months after therapy. Major cardiac event risk during 3 years of follow-up was calculated using an equation based on that in the J-ACCESS study. Patients with ≥ 10% cardiac event risk estimated at the first MPS (n = 31) were analyzed and followed up for at least 1 year. RESULTS: Estimated risk was reduced by ≥ 5% in 14 patients (45%) after therapy. During a follow-up period of 22.1 ± 6.7 months, one patient without such reduction had a major cardiac event. Mean %summed stress scores significantly decreased from baseline to follow-up in patients with and without risk reduction. Left ventricular ejection fraction (LVEF [%]) at rest was significantly increased at the second, compared with the first MPS between patients with, than without risk reduction (57 ± 17 vs. 45 ± 16%, p = 0.001 and 50 ± 11 vs. 49 ± 9%, p = 0.953, respectively). CONCLUSIONS: A reduction in cardiac ischemia and an increase in LVEF by revascularization and/or OMT were necessary to avoid cardiac events among patients with moderate-to-high estimated risk, and changes in event risk were quantifiable.

Predictive value of electrocardiography-gated myocardial perfusion imaging to new-onset heart failure in patients with chronic kidney disease: findings from the J-ACCESS 3 study.

The incidence of heart failure (HF) increases in patients with chronic kidney disease (CKD). Factors that could predict patients with CKD who are at high risk for developing HF should be identified. We analysed clinical parameters and stress/rest myocardial perfusion imaging (MPI) findings derived from 499 patients with CKD by the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT 3 (J-ACCESS 3) to clarify predictors of new-onset HF. Forty-one patients with congestive HF in the J-ACCESS 3 database were followed up for three years. Multivariable Cox hazards models selected haemoglobin (hazard ratio [HR] 0.809; 95% confidence interval [CI] 0.679-0.964), summed stress score (HR 1.082; 95% CI 1.016-1.151) and left ventricular ejection fraction (HR 0.970; 95% CI 0.949-0.992) as independent predictors of new-onset HF. Haemoglobin combined with summed stress scores and ejection fraction had the greatest incremental prognostic value over any one or more combined factors (global χ2, 29.9). Anaemia, stress-induced myocardial ischaemia, and left ventricular contraction are independent predictors of risk of new-onset HF in patients with CKD. Stress/rest MPI provides additional information with which to identify patients with CKD at greater risk of new-onset HF.

Risk stratification based on J-ACCESS risk models with myocardial perfusion imaging: Risk versus outcomes of patients with chronic kidney disease.

BACKGROUND: This study aimed to validate the accuracy of major-event risk models created in the multicenter J-ACCESS prognostic study in a new cohort of patients with chronic kidney disease (CKD). METHODS AND RESULTS: Three multivariable J-ACCESS risk models were created to predict major cardiac events (cardiac death, non-fatal acute coronary syndrome, and severe heart failure requiring hospitalization): Model 1, four variables of age, summed stress score, left ventricular ejection fraction and diabetes; Model 2 with five variables including estimated glomerular filtration rate (eGFR, continuous); and Model 3 with categorical eGFR. The validation data used three-year (3y) cohort of patients with CKD (n = 526, major events 11.2%). Survival analysis of low (< 3%/3y), intermediate (3% to 9%/3y), and high (> 9%/3y)-risk groups showed good stratification by all three models (actual event rates: 3.1%, 9.9%, and 15.9% in the three groups with eGFR ≥ 15 mL/min/1.73 m2, P = .0087 (Model 2). However, actual event rates were equally high across all risk groups of patients with eGFR < 15 mL/min/1.73 m2. CONCLUSION: The J-ACCESS risk models can stratify patients with CKD and eGFR ≥ 15 mL/min/1.73 m2, but patients with eGFR < 15 mL/min/1.73 m2 are potentially at high risk regardless of estimated risk values.

The difference of risk factors predicting cardiac events in patients with chronic kidney disease between with and without diabetes.

OBJECTIVE: Chronic kidney disease (CKD) and diabetes are both associated with cardiovascular disease, but the effects of diabetes in patients with CKD remain unknown. This study aimed to compare the risk factors of cardiac events between patients with CKD accompanied and not by diabetes using myocardial perfusion imaging. METHODS: We initially classified 529 patients with CKD from the Japanese Assessment of Cardiac Events and Survival Study-3 (J-ACCESS-3) study who had been assessed by gated single-photon emission-computed tomography based on whether they had diabetes (n = 220) or not (n = 309) and then separated them into four subgroups based on the ejection fraction (EF) calculated by quantitative gated SPECT. After 3-year follow-up, the incidence of major cardiac events (cardiac death, sudden death, non-fatal myocardial infarction, and heart failure requiring hospitalization), risk factors among each group, and the ability of myocardial perfusion image to predict prognosis were evaluated. RESULTS: Major cardiac events occurred in 12.7% and 10.3% of patients with and without diabetes (not significant), and heart failure requiring hospitalization was the most frequent (75% and 78%, respectively) in both groups. Event-free survival rates were lower in the subgroups with low EF and high summed stress scores (SSS). Independent risk factors comprised currently smoking and a higher SSS, among patients with diabetes, while higher left ventricular end diastolic volumes and serum C-reactive protein values among those without diabetes. CONCLUSIONS: In patients with CKD, while the risk factors of major cardiac events differ between in patients with and without diabetes, quantitation with gated MPI could be used effectively in both groups.

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.

Prognostic value of normal stress myocardial perfusion imaging and ventricular function in Japanese patients with chronic kidney disease: a study based on the J-ACCESS-3 database.

BACKGROUND: The purpose of this study is to test the hypothesis that a normal myocardial perfusion imaging (MPI) study in chronic kidney disease (CKD) can provide benign prognostic information for the prediction of major cardiovascular events. METHODS: The study group consisted of 431 CKD patients (males, 64%; mean age, 72 ± 11 years) with normal SPECT imaging. Based on SPECT image and QGS data, 331 had a summed stress score of 3 or less, a summed difference score of 1 or less and normal cardiac function (males; end-systolic volume (ESV) ≤ 60 ml, females; ESV ≤ 40 ml, males, ejection fraction (EF) ≥ 49%; females, EF ≥ 50%). RESULTS: During a 3-year follow-up period, there were a total of 27 major cardiovascular events, including cardiac death (n = 3), sudden death (n = 3), and acute coronary syndrome (n = 3), and 19 were hospitalized because of congestive heart failure. Kaplan-Meier analysis showed that the number of major cardiovascular events in patients with higher eGFR of ≥ 15 ml/min) were very few, and regarded as low risk. According to the eGFR status, namely < 15 (n = 58), 15 to < 30 (n = 97), 30 to < 45 (n = 131), ≥ 45 (n = 45), the higher cardiac event rate was observed in patients with eGFR of < 15 ml/min among the four groups. The major cardiovascular event rate in patients with the lowest eGFR (< 15) was twice as much than that in patients with eGFR of ≥ 30 ml/min. Lower hemoglobin (males, < 12 g/dl; females, < 11 g/dl) and higher CRP (CPR ≥ 0.3 mg/dl) were also the predictors of increased risk. CONCLUSIONS: Normal stress SPECT images confer a benign prognosis in patients with CKD, but care must be taken for severely reduced renal function, which was associated with higher cardiac event.

Cardiac event risk stratification in patients with end-stage renal disease: Sub-analysis of the B-SAFE study.

BACKGROUND: The aim of this study was to investigate whether 123I-labelled ß-methyl iodophenyl-pentadecanoic acid (BMIPP) imaging as an abnormal myocardial fatty acid metabolism indicator better predicted fatal and non-fatal cardiac events than conventional predictors [e.g. peripheral artery disease (PAD) and diabetes mellitus (DM)] in haemodialysis patients. METHODS: In a sub-analysis of the BMIPP SPECT Analysis for Decreasing Cardiac Events in Haemodialysis Patients (B-SAFE) study, 677 asymptomatic patients with ≥1 cardiovascular risk factor and without known coronary artery disease were followed for 3 years. The amount of radioactivity in each 17-left ventricular segment was graded visually and assigned a score from 0 (normal) to 4 (absent). Its total values were designated as baseline summed BMIPP scores. Outcome measures were composite cardiac events. RESULTS: Cardiac events correlated with age, PAD [hazard ratio (HR): 2.15; p=0.003], DM (HR: 1.76; p=0.006) and summed BMIPP scores (4-8, HR: 1.82; p<0.001; ≥9, HR: 3.49; p<0.001). Cardiac event-free rates decreased with increasing summed BMIPP scores, PAD and DM. Areas under the receiver operating curves (AUCs) indicated that a BMIPP-based model (AUC: 0.656) was more predictive than DM or PAD models (AUC: 0.591); a model with all three was most predictive (AUC: 0.708). The three-year cardiac event-free rates significantly decreased in patients with PAD and/or DM in all summed BMIPP score categories. CONCLUSIONS: Abnormal myocardial fatty acid metabolism strongly predicts cardiac events in haemodialysis patients; those with PAD or DM are at high risk for cardiac events.

Sudden death prediction by C-reactive protein, electrocardiographic findings, and myocardial fatty acid uptake in haemodialysis patients: analysis of a multicentre prospective cohort sub-study.

AIMS: The purpose of this study was to identify determinants of sudden death among clinical information in combination with cardiac fatty acid metabolism for better risk-stratification of haemodialysis patients. METHODS AND RESULTS: Clinical and imaging data from 677 haemodialysis patients enrolled in the beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) SPECT Analysis for Decreasing Cardiac Events in Hemodialysis Patients (B-SAFE) study were analysed in this study. During a 3-year prospective follow-up interval, 20 sudden deaths were observed. Compared with non-sudden death patients, sudden death patients more frequently had an increased C-reactive protein level (>2.38 mg/dL), electrocardiographic abnormal Q-wave and increased BMIPP abnormality score (>16). Patients with BMIPP score >16 and at least one of the other predictors had significantly lower event-free rates than did those without the BMIPP abnormality (P < 0.001). Univariate and multivariate Cox regression analyses revealed increased C-reactive protein level, abnormal Q-wave, and greater BMIPP abnormality as significant sudden death predictors with hazards ratios of 6.83 (95% CI: 1.76-26.47, P = 0.005), 17.73 (95% CI: 4.91-63.98, P < 0.001), and 10.58 (95% CI; 3.84-29.14, P < 0.001), respectively. The addition of BMIPP score >16 to the other clinical predictors increased the hazard ratio and receiver-operating characteristic analysis-area under the curve up to 145.22 (95% CI; 0.34-695.09) and to 0.677-0.690, respectively. CONCLUSIONS: Increased C-reactive protein, electrocardiographic Q-wave, and impaired myocardial fatty acid metabolism are independently and synergistically related to sudden death risk in haemodialysis patients. The non-invasive strategy presented here might contribute to the identification of haemodialysis patients who can most benefit from a prophylactic treatment against sudden death.

Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.

BACKGROUND: The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. METHODS AND RESULTS: A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled ß-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. CONCLUSIONS: Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.

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.

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

BACKGROUND: The findings of our recent study entitled, "Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS)" showed that myocardial perfusion single photon emission computed tomography (MPS) can detect coronary artery disease (CAD) and help to predict future cardiac events in patients with suspected or extant CAD. However, the extent of the benefit conferred by percutaneous coronary intervention (PCI) as an initial management strategy compared with optimal medical therapy remains controversial. Little evidence supports the notion that myocardial ischemia identified using MPS is an alternative target of coronary revascularization to reduce the likelihood of developing cardiac events. METHODS: The multicenter, prospective cohort J-ACCESS 4 study aims to clarify the prognostic impact of reducing myocardial ischemia determined using electrocardiogram-gated MPS in Japanese patients with coronary artery disease. We started to register patients in J-ACCESS 4 at 74 facilities during June 2012 and will continue to do so until December 2013 or until the cohort comprises 500 patients who will participate in the study from one month before, until two months after stress/rest MPS assessment. Imaging data, the background of the patients including coronary risk factors and treatment before MPS assessments will be analyzed. The patients will undergo coronary revascularization within two months after MPS and/or receive appropriate medical therapy. The second stress/rest MPS will be performed from 4 to 10 months after coronary revascularization or registration. They will be followed up for over one year after the second MPS assessment. The primary endpoints will be cardiac death, sudden death of unknown cause, non-fatal myocardial infarction, and hospitalization for heart failure. The secondary endpoints will comprise death due to all causes including non-cardiac death and any cardiovascular events. This study will be completed in 2015. Here, we describe the design of the J-ACCESS 4 study.

Successful removal of a Gunther tulip vena cava filter with wall-embedded hook and migration during a retrieval attempt.

Retrieval of a Gunther tulip vena cava filter implanted in a patient with inferior vena cava and right common iliac vein thrombosis was attempted by the standard method. Because the filter was tilted, the hook became attached to the vena cava wall and could not be snared. During attempts at removal by an alternative method, the filter migrated toward the right atrium. However, it was finally successfully removed.

Prognostic value of myocardial perfusion imaging for cardiovascular events among asymptomatic Japanese patients with type 2 diabetes and mild renal dysfunction.

BACKGROUND: Diabetes is frequently accompanied by chronic kidney disease, and both diabetes and chronic kidney disease are risk factors for ischemic heart disease; however, cardiac risk among diabetic patients with mild renal dysfunction has not been analyzed in detail. The present study investigates how myocardial perfusion imaging (MPI) contributes to the risk stratification of diabetic patients with mild renal dysfunction who are asymptomatic for cardiac diseases. PATIENTS AND METHODS: Among 513 asymptomatic patients with type 2 diabetes in the Japanese Assessment of Cardiac Events and Survival Study 2 (J-ACCESS) database, we selected 286 with estimated glomerular filtration rates (eGFR) of at least 45 ml/min/1.73 m and assigned them to groups on the basis of eGFR of at least 60 without (group A, n=66) or with microalbuminuria or eGFR 45 to less than 60 (group B, n=220). The 3-year incidence of cardiac events and the value of MPI were evaluated. RESULTS: Cardiac events developed in 1.52 and 4.55% of patients in groups A and B, respectively. Event-free survival did not differ according to summed stress scores in group A but was significantly lower among patients with summed stress scores of at least 9 in group B. CONCLUSION: Routine MPI might be useful for stratifying risk among diabetic patients with mild renal dysfunction but is unnecessary for those with good renal function.

Metabolic syndrome is not a predictor for cardiovascular events in Japanese patients with diabetes mellitus asymptomatic for coronary artery disease: a retrospective analysis of the J-ACCESS-2 study.

PURPOSE: Patients with metabolic syndrome (MetS) have potentially higher risk for cardiovascular events. The aim of this study was to evaluate the effect of MetS on cardiac events in type-2 diabetic patients asymptomatic for coronary artery disease (CAD) in a Japanese population. METHODS: A total of 485 patients from a J-ACCESS-2 investigation with stress-gated myocardial perfusion imaging (MPI) and quantitative-gated MPI analysis were examined. Cardiovascular hard events (cardiac death and acute coronary syndrome) and total events during a 3-year follow-up were analyzed. RESULTS: The MetS group (n = 229) had higher incidence of hypertension, dyslipidemia, and ventricular dilatation than the non-MetS group (n = 256). The hard events were 8 and 12 for the MetS and non-MetS groups (P = n.s.), and total events were 31 and 31 for each of these groups, respectively (P = n.s.). Significant variables related to total cardiovascular events included age, current smoking, insulin use, total cholesterol, ejection fraction, summed stress score ≥ 9, and summed difference score ≥ 2. Cox proportional hazard analysis and Kaplan-Meier survival analysis showed that only the summed stress score was related to total events (P = .01), and the presence and the number of items for MetS criteria were not. CONCLUSION: In patients with type 2 diabetes asymptomatic for CAD, cardiovascular events and ischemia are as common in diabetic patients without MetS as in those with MetS. A high MPI defect score is related to total events including cardiac and cerebrovascular events.

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.

Improved lipid profiles are associated with reduced incidence of coronary vascular events in asymptomatic patients with type 2 diabetes and impaired myocardial perfusion.

AIM: Individuals with type 2 diabetes are at high risk for cardiovascular events; however, a modality that could reduce risk has not been fully evaluated. We examined the annual incidence rate of cardiovascular events in asymptomatic Japanese diabetic patients who underwent gated myocardial perfusion single-photon computed tomography (SPECT). METHODS: Asymptomatic patients (n= 485) aged ≥50 years and with either a maximal carotid artery intima-media thickness of ≥1.1 mm, or urinary albumin ≥30 mg/g creatinine, or at least two of abdominal obesity, low HDL cholesterol, high triglyceride levels and hypertension were evaluated at 50 institutions using gated SPECT with the stress-rest protocol and were followed up for three years. In the patients with summed stress scores (SSS) of ≥9, the initial high cardiovascular incidence rate in the first year declined significantly (p<0.001) from 21% to 2% during the second and third year. RESULTS: The incident rate was consistent among diabetics with low SSS during follow-up. Baseline LDL and non-HDL cholesterol levels significantly reduced (123±6.4 to 99±6.1 mg/dL; p<0.05) during the first year in diabetic patients with high SSS, but did not significantly change in diabetic patients with low (<9) SSS. CONCLUSION: The immediate improvement of lipid levels within one year correlated with the significant reduction in CVD events arising in diabetic patients with moderate or severe myocardial ischemia. Thus, rapidly lowering hyperlipidemia is very effective for patients with type 2 diabetes at high risk for cardiac events.