Normal limits of ejection fraction and volumes determined by gated SPECT in clinically normal patients without cardiac events: A study based on the J-ACCESS database

金沢大学大学院医学系研究科がん制御学Purpose: Quantitative gated single-photon emission computed tomography (SPECT) is known to have high accuracy and precision for measurement of the principal cardiac functional parameters. We hypothesised that normal values for EF and LV volumes may differ among nationalities, and that optimal threshold values specific to the study population are required. Methods: Among 4,670 consecutively registered patients for a J-ACCESS (Japanese investigation regarding prognosis based on gated SPECT) study from 117 hospitals, a total of 268 (149 women, 119 men) were selected who had no baseline cardiac diseases and had experienced no cardiac events during the preceding 3-year period. A gated SPECT study was performed with 99mTc-tetrofosmin and analysed with Cedars Sinai Medical Center\u27s quantitative gated SPECT (QGS) software. The results in respect of ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), and EDV, ESV and SV normalised by body surface area (EDVI, ESVI and SVI), were calculated and summarised to obtain normal limits. Results: EF for women and men was 74 ± 9% and 63 ± 7%, respectively (p < 0.0001). EDV, ESV and SV were significantly smaller in women than in men. Based on multiple regressions for linear models, the primary and secondary predictors of EF, EDVI, ESVI were gender and age. By stepwise multiple regression analysis, a statistically significant third predictor for EDV, ESV, SV and SVI was body weight. No colinearity was found between age and body weight. Important factors for the studied Japanese population included a high incidence of small hearts in women and the relatively advanced age of the population (the mean age ±SD was 64.1 ± 10.0 years for women and 60.9 ± 11.7 years for men). Conclusion: EF and volumes determined by gated SPECT with QGS were significantly affected by gender and age, with body weight as a third predictor for volumes. Moreover, the normal limits were so specific for the population studied that standards appropriate for the study in question should be utilised. © 2007 Springer-Verlag

Prognostic value of myocardial perfusion and ventricular function in a Japanese multicenter cohort study (J-ACCESS): the first-year total events and hard events

金沢大学医薬保健研究域医学系Objective: To determine the prognostic value of myocardial ischemia, function and coronary risk factors on total and hard cardiac events using myocardial perfusion imaging in a Japanese population. Methods: A prospective cohort study was performed in 117 Japanese hospitals, each with a nuclear cardiology facility. A total of 4,031 patients with suspected or confirmed ischemic heart disease were registered. The patients were followed up for a year to investigate total and hard events, and those who had any events were followed up for 3 years to evaluate subsequent hard events. A stress-rest gated myocardial perfusion study was performed with 99mTc-tetrofosmin using gated single-photon emission computed tomography (SPECT) and analyzed by semi-quantitative scores. Results: During the 1-year follow-up period, 263 (6.5%) patients had total events comprising all-cause death, non-fatal myocardial infarction (MI), heart failure, unstable angina, angina pectoris and coronary revascularization. Cardiac death occurred in 23 patients (0.6%) and non-fatal MI in 11 (0.3%). Among patients with ejection fraction (EF) of <45% and a summed difference score (SDS) of ≥2, 18.7% (2.4% for cardiac death and 0.6% for non-fatal MI) experienced total events compared with 3.9% (0.3% for cardiac death and 0.2% for non-fatal MI; P < 0.0001) of those with EF ≥ 45% and SDS < 2. Multivariate analysis identified EF, SDS, age, history of revascularization and diabetes as significant predictors of all events, while the significant predictors were age and EF for hard events. When the patients who had heart failure in the first year were followed up, 9 of 41 (22.0%) experienced cardiac death in the subsequent 3-year follow-up period. Conclusions: Myocardial ischemia defined by SDS and ventricular function were the main predictors of total events despite the relatively low incidence of hard events in this Japanese population. In patients with cardiac events in a year, closer attention should be paid to subsequent hard events particularly in patients with heart failure. © 2009 The Japanese Society of Nuclear Medicine

Important parameters in the detection of left main trunk disease using stress myocardial perfusion imaging

SummaryObjectivesWe sought noninvasively to diagnose left main trunk (LMT) disease using myocardial perfusion imaging (MPI).MethodsFive hundred and eight patients with suspected coronary artery disease (CAD) underwent both stress MPI and coronary angiography. The extent and severity of perfusion abnormalities were assessed using a 20-segment model. In addition, perfusion defects in both left anterior descending and left circumflex arterial territories were defined as a left main (LM) pattern defect, and those in 3-coronary arterial territories as a 3-vessel pattern defect.ResultsIn 42 patients with LMT disease, a summed stress score (19.4±10.0 vs. 13.5±10.0; p<0.0001) and a summed rest score (12.1±9.7 vs. 7.0±7.8; p=0.002) were greater than in 466 patients without LMT disease, while a summed difference score was similar (7.3±7.7 vs. 6.5±6.1; p=NS). The prevalence of an LM-pattern defect was low in both groups (12% vs. 8%; p=NS). However, a 3-vessel pattern defect (33% vs. 7%; p<0.0001), lung uptake of radiotracers (38% vs. 11%; p<0.0001), and transient ischemic dilation (31% vs. 13%; p=0.003) were more frequently observed in patients with LMT disease than in those without. Logistic regression analysis showed that a 3-vessel pattern defect (OR=3.5, 95% CI=1.4–8.8; p=0.007), lung uptake of radiotracers (OR=2.5, 95% CI=1.1–5.7; p=0.03), and previous myocardial infarction (MI) (OR=2.4, 95% CI=1.0–5.7; p=0.05) were the most important parameters to detect LMT disease. After excluding 163 patients with previous MI, a repeat analysis revealed that lung uptake of radiotracers (OR=8.2, 95% CI=2.3–29.2; p=0.001) and an LM-pattern defect (OR=6.3, 95% CI=1.4–27.2; p<0.02) were independent predictors for LMT disease.ConclusionIn the identification of LMT disease, lung uptake of radiotracers was a single best parameter, which was independent of the presence or absence of previous MI

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan

金沢大学医薬保健研究域医学系Backgrounds: Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. Methods: A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using 99mTc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 ± 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. Results: Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 ± 17% and 55 ± 18%, p < 0.0001 for non-gated; 64 ± 16% and 51 ± 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. Conclusion: Segmental 99mTc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study. © 2008 Springer-Verlag

Rationale and design of a randomized trial to test the safety and non‑inferiority of canagliflozin in patients with diabetes with chronic heart failure : the CANDLE trial

Background: Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure. Methods: A total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function. Discussion: The CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure

Longitudinal association among endothelial function, arterial stiffness and subclinical organ damage in hypertension

Objectives: To examine the longitudinal mutual association between endothelial dysfunction and arterial stiffness, and also to determine which of the two variables was more closely associated with the progression of subclinical organ damage. Methods: The brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria and flow-mediated vasodilatation of the brachial artery (FMD) were measured three times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive treatment. Results: The change of the baPWV during the study period was larger in the subjects with baseline FMD values in the lowest tertile as compared to those with baseline FMD values in the highest tertile. The change of the CIMT was smaller in the subjects with baseline baPWV values in the lowest tertile than in those with baseline baPWV values in the highest tertile. After the adjustment, the FMD value at the baseline was inversely associated with the baPWV at the end of the study period (beta = − 0.07, p = 0.01), although, the reverse association was not significant. The baPWV, but not the FMD value, at the baseline was associated with the CIMT (beta = 0.06, p = 0.04) measured at the end of the study period. Conclusions: In hypertension, endothelial dysfunction was associated with the progression of arterial stiffness, although the reverse association was not confirmed. The increased arterial stiffness rather than endothelial dysfunction may be more closely associated with the progression of atherosclerotic vascular damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis continuum may be important in hypertension

Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese

Aims: For the standardization of flow-mediated vasodilatation (FMD) assessment as a clinical tool, validation of its reliability across multiple institutions and the establishment of normal/reference values based on reliable data from multiple institutions are needed. Methods and results: In Study 1, assessment of FMD (scan recording and analysis) using an ultrasonographic semi-automatic measuring system (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All of the brachial arterial scans were also analyzed at a core laboratory (sFMD-COLB). After 111 subjects with inadequate sFMD recordings were excluded (n = 880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725 to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD from 27 institutions, reference values of sFMD are proposed by the Framingham risk score (FRS)-based risk categories and according to gender and age. The receiver-operating characteristic curve analysis revealed a significant power of sFMD values in reference ranges to discriminate between subjects with and without CVD (e.g., area under curve = 0.64 in the FRS-low risk group). Conclusions: When the analysis was limited to cases with clear sFMD recordings, the reliability of the sFMD assessment (scan and its analysis) conducted in individual institutions appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the Japanese population are proposed based on reliable data derived from multiple institutions, and the reference values may identify patients without advanced vascular damage