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Coronary spastic angina (CSA) in premenopausal women is rare, but has also been suggested to be associated with estrogen decline during the menstrual cycle. In this report, we describe the case of a young premenopausal patient with refractory CSA. She presented with ventricular fibrillation (VF) at the age of 15 years and was diagnosed as having CSA. She underwent implantation of an Implantable Cardioverter Defibrillator (ICD), and despite receiving systemic drug therapy at the maximum doses, she experienced a total of four appropriate ICD shocks over the subsequent six years. Based on careful history-taking, it was suspected that the angina episodes were closely related to the phase of the menstrual cycle. We started the patient on continuous combined estrogen-progestin hormone contraception therapy so as to prevent the reduction of the blood estrogen levels just prior to and during menstruation. After the start of this treatment, the patient became completely free of angina episodes. Although there are a few reports of the efficacy of hormone replacement therapy in premenopausal women with CSA, this is the first report of the efficacy of this therapy in a woman as young as 22 years old. < Learning objective: There are a few reports of episodes of CSA occurring in relation to the phase of the menstrual cycle in premenopausal women. It is considered to be associated with decline of the blood estrogen levels and combined estrogen plus progestin contraception therapy may be effective in such cases.>., (© 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index β-transformed value (β-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P <0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P <0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects.

Background: This randomized, double-blind, placebo-controlled, cross-over study was conducted to examine the effects of lactotripeptide supplementation on 7-day mean tele-monitored home blood pressure (BP), and also on the markers of vascular function and renal damage in Japanese subjects with prehypertension. Methods and Results: A total of 26 subjects with prehypertension were randomly allocated to receive the active product (lactotripeptide tablet) or a placebo tablet for 8 weeks each in a cross-over manner. Urinary liver-type fatty acid-binding protein-to-creatine ratio (UFABPCR) and vascular function were measured at the end of each intervention. Home systolic and diastolic BP at the end of the lactotripeptide supplementation period was significantly lower than that at the end of the placebo period (P<0.05). On mixed linear model analysis there was a significant difference in the change in home diastolic BP after intervention between the 2 interventions (P=0.04). UFABPCR was significantly lower at the end of the lactotripeptide intervention period than at the end of the placebo period (P<0.05). Conclusions: The beneficial effect of lactotripeptide supplementation on 7-day mean tele-monitored home BP was confirmed in Japanese subjects with prehypertension. In addition, this intervention also seemed to have a protective effect against the progression of renal function decline., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Background: The precise mechanisms underlying elevation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy subjects have not been fully clarified. Methods and Results: In 2,844 Japanese healthy subjects with serum NT-proBNP <125 pg/mL, (1) brachial-ankle pulse wave velocity and (2) second peak of the peripheral systolic blood pressure minus diastolic blood pressure (pulse pressure 2 [PP2]), as markers of cardiac afterload; (3) fibrosis 4 score (FIB-4 score, a marker of liver fibrosis), as a marker of cardiac preload; and (4) ratio of the pre-ejection time to ejection time (PEP/ET), as a marker of cardiac systolic function, were measured. At the first examination, after the adjustments, log-transformed serum NT-proBNP was associated with PP2 and FIB-4 score, but not with PEP/ET. These parameters were successfully measured again after a 3-year interval in 1,978 subjects. On Pearson's correlation analysis, change in PP2 and FIB-4 score during the study period was significantly correlated with change in serum NT-proBNP (r=0.05, 0.09, respectively; P<0.01). Conclusions: In apparently healthy Japanese subjects, both increased cardiac preload and increased cardiac afterload, but not impaired cardiac systolic function, may be associated with elevated serum NT-proBNP., Competing Interests: With regard to the employee data, the sponsor (Omron Health Care Company) assisted in the data formatting (i.e., the data of the brachial-ankle pulse wave velocity stored in the hard disc of the equipment used for measurement of the brachial-ankle pulse wave velocity was transferred to an Excel file). Other than this, however, the company played no role in the design or conduct of the study, that is, in the data collection, management, analysis or interpretation of the data, or in the preparation, review or approval of the manuscript. The authors declare no other conflicts of interest., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Aims: Pulmonary congestion is associated with poor prognosis following hospitalization for worsening heart failure (HF), although its quantification and optimal timing during HF hospitalization remains challenging. The aim of this study was to assess the prognostic value of radiographic pulmonary congestion at admission and discharge in patients with worsening HF., Methods and Results: Clinical, echocardiographic, laboratory and chest X-ray data of 292 acute decompensated HF patients were retrospectively studied (follow-up 1 year). Lung congestion was blindly scored on chest X-ray performed at admission and discharge using a systematic 6-zone approach. Primary clinical outcome was a composite outcome of re-hospitalization for worsening HF or all cause death. Patients were stratified according to the median of congestion score index (CSI) at both admission (median CSI(A) = 1.33) and discharge (median CSI(D) = 0.33). BNP levels, LVEF and eGFR did not differ between CSI categories. In multivariable Cox regression analysis, discharge CSI (HR for 1-point increase = 1.83 [1.02 to 3.27] p = 0.04) and discharge BNP were significantly associated with the composite outcome whereas NYHA class, physical signs, admission CSI and echocardiographic data were not. Furthermore, discharge CSI significantly increased reclassification on top of clinical covariates (continuous NRI = 19.6% [4.0 to 30.0] p = 0.03 and IDI = 2.2% [0.0 to 7.6] p = 0.046) while discharge BNP did not significantly improve risk reclassification., Conclusions: Residual pulmonary congestion assessed by radiographic scoring predicts poor prognosis beyond physical assessment, echocardiographic parameters and BNP. These findings further support the capital prognostic value of radiographic pulmonary congestion in patients hospitalized for worsening HF., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear., Methods and results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model., Conclusions: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. This study aimed to reveal the clinical and genetic backgrounds of the unique HCM with mid-ventricular obstruction (HCM-MVO) subtype. We identified 34 patients with HCM-MVO in our cohort, and about half (47%) of these patients experienced adverse events. We analyzed 67 cardiomyopathy-associated genes in the patients. In total, 44% of patients with HCM-MVO carried the cardiomyopathy-associated genetic variant (CAGV) in 14 genes. Only 21% of patients carried HCM-associated CAGVs in major sarcomere-encoding genes, while 18% of patients carried CAGVs in dilated cardiomyopathy/arrhythmogenic right ventricular cardiomyopathy-associated genes. CAGVs were more frequent in patients with asymmetric septal hypertrophy (ASH) than in those without ASH. These findings suggest that HCM-MVO is a high-risk group and may have different etiologies from typical HCM.

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 99m Tc-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% ± 10.7% vs. 65.4% ± 11.3%; p < 0.001) but not at rest (67.1% ± 11.3% vs. 68.3% ± 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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

This study analyzed repeated measurement data to clarify the longitudinal associations between hyperuricemia and the risk factors for the development of hypertension (ie, increased arterial stiffness, renal dysfunction, and inflammation), and then examined whether these risk factors show longitudinal associations with the development of hypertension. In 3274 Japanese men without hypertension, the brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum uric acid and CRP (C-reactive protein) levels were measured annually over an 8-year period. Of these, 474 subjects developed hypertension by the end of the study period. Mixed model linear regression analysis revealed a significant longitudinal association of hyperuricemia with increase of the brachial-ankle pulse wave velocity (estimate=5.50, P=0.04), decrease of the estimated glomerular filtration rate (estimate=-2.02, P<0.01), and elevation of the CRP (estimate=0.08×10 -1 , P=0.02). Hyperuricemia at the study baseline was associated with a significant odds ratio for the development of hypertension by the end of the study period. After adjustments for covariates, the brachial-ankle pulse wave velocity (estimate=0.51×10 -2 , P<0.01) and CRP (estimate=1.91, P=0.03), but not estimated glomerular filtration rate, were found to show independent longitudinal associations with the new onset of hypertension. In Japanese men without hypertension, hyperuricemia may have a longitudinal association with the development of hypertension, and increased arterials stiffness and inflammation may be involved in the risk of development of hypertension associated with hyperuricemia.

Background: It remains to be clarified whether liver stiffness is a direct risk factor for heart failure (HF) or whether its association with HF is mediated by vascular damage. We conducted cross-sectional and prospective longitudinal studies to examine whether fibrosis 4 score (FIB-4 score) is directly associated with the serum NT-pro-BNP levels or the association is mediated by arterial stiffness and/or abnormal central hemodynamics., Methods and Results: In 3040 health Japanese subjects with serum NT-pro-BNP levels < 125 pg/ml, the FIB-4 score was calculated, and the serum NT-pro-BNP levels, brachial-ankle pulse wave (baPWV) velocity and radial augmentation index (rAI) were measured. These parameters were measured again after a 3-year interval in 2135 subjects. Multivariate linear regression analysis demonstrated a significant cross-sectional association of the FIB-4 scores with the log-transformed the serum NT-pro-BNP levels (beta = 0.08, p  < 0.01), but not with the baPWV or rAI. The change of serum NT-pro BNP levels during the study period was significantly higher in subjects with increase of the FIB-4 score during the study period (8.2 ± 22.5 pg/ml) than that in those with decrease/no change (5.4 ± 22.3 pg/ml) ( p  < 0.05)., Conclusion: Liver stiffness may have a significant direct association with the development of HF from the early stage, without the mediation of arterial stiffness and/or abnormal central hemodynamics. Therefore, the FIB-4 score appears to serve as a direct risk factor for HF from the early stage, and its association with HF may not be mediated by vascular damages.

Background: Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is frequent finding in hospitalized heart failure (HHF), its impact on long-term outcome in HHF patients remains unclear., Methods: We evaluated iron status at discharge in 578 HHF patients. Absolute ID was defined as serum ferritin <100 μg/L, and functional ID (FID) was defined as serum ferritin of 100-299 μg/L with transferrin saturation <20%. The primary outcome of interest was the composite of all-cause mortality and HF admission at one year., Results: Among the study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID. At one-year post-discharge, 64 patients had died and 112 had been readmitted with HF. Patients with absolute ID had more adverse events than those with FID or no ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was significantly associated with increased risk of adverse events at one year (HR 1.50, 95% CI 1.02-2.21, p = 0.040) compared with the remaining patients. Sensitivity analysis revealed that its prognostic effect did not differ across anemic status, or between HF with reduced and preserved ejection fraction (p for interaction = 0.17, 0.68, respectively)., Conclusion: Absolute ID, but not FID, at discharge was associated with increased risk of one-year mortality or HF admission in patients with HHF. Further studies are required to evaluate the role of repleting iron stores and its impact on clinical outcomes in patients with HHF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We conducted analyses of repeated-measures data to examine whether pressure wave reflection acts additively or synergistically with arterial stiffness in the pathogenesis of hypertension., Methods and Results: In 3172 middle-aged (42±9 years) healthy Japanese men without hypertension at the study baseline, systolic and diastolic blood pressures, brachial-ankle pulse wave velocity, and radial augmentation index were measured annually during a 9-year study period. Of these, 474 participants (15%) developed hypertension by the end of the study period. Binary logistic regression analysis demonstrated significant individual odds ratios for both baseline brachial-ankle pulse wave velocity and radial augmentation index for the development of hypertension. The rate of onset of hypertension during the study period was highest in the participant group with high values for both brachial-ankle pulse wave velocity and radial augmentation index at study baseline (262 of 965 participants: 27%). The generalized estimating equation analysis revealed that both radial augmentation index (estimate=0.06, SE=0.03, P =0.05) and brachial-ankle pulse wave velocity (estimate=0.07×10 -1 , SE=0.02×10 -1 , P <0.01) showed significant longitudinal association with new onset of hypertension, with no significant interaction., Conclusions: In Japanese men, abnormal wave reflection and increased arterial stiffness may be additively associated with the risk of new onset of hypertension. Abnormal wave reflection and elevated central blood pressure may be longitudinally associated with increase in arterial stiffness, and this longitudinal association may be a mechanism underlying the additive effect of these 2 variables on the risk of new onset of hypertension., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

We investigated the effects of caffeine intake on fractional flow reserve (FFR) values measured using intravenous adenosine triphosphate (ATP) before cardiac catheterization. Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values. Patients were evenly randomized into 2 groups preceding the FFR study. In the caffeine group (n = 15), participants were given coffee containing 222 mg of caffeine 2 h before the catheterization. In the non-caffeine group (n = 15), participants were instructed not to take any caffeine-containing drinks or foods for at least 12 h before the catheterization. FFR was performed in patients with more than intermediate coronary stenosis using the intravenous infusion of ATP at 140 μg/kg/min (normal dose) and 170 μg/kg/min (high dose), and the intracoronary infusion of papaverine. FFR was followed for 30 s after maximal hyperemia. In the non-caffeine group, the FFR values measured with ATP infusion were not significantly different from those measured with papaverine infusion. However, in the caffeine group, the FFR values were significantly higher after ATP infusion than after papaverine infusion (P = 0.002 and P = 0.007, at normal and high dose ATP vs. papaverine, respectively). FFR values with ATP infusion were significantly increased 30 s after maximal hyperemia (P = 0.001 and P < 0.001 for normal and high dose ATP, respectively). The stability of the FFR values using papaverine showed no significant difference between the 2 groups. Caffeine intake before the FFR study affected FFR values and their stability. These effects could not be reversed by an increased ATP dose.

Background: Recently, a simple parameter calculated from the brachial pressure waveform recorded using an oscillometric device (arterial velocity pulse index [AVI]: ratio of the forward/reflected pressure wave amplitudes) has become available to assess the pathophysiological abnormalities associated with vascular damage. Peripheral artery disease (PAD) represents one of the disease entities associated with the advanced stages of atherosclerotic vascular damage. The present study was conducted to examine whether an increase in the AVI might be influenced by the presence of PAD., Methods and Results: The AVI was measured from oscillometric recordings of the brachial pressure waveform, and the ankle-brachial pressure index (ABPI) was determined by an oscillometric method. Study 1: In 341 consecutive patients admitted for the management of cardiovascular disease and/or cardiovascular risk factors, the ABPI and the AVI were measured simultaneously. An ABPI ≤0.90 was observed in 19 subjects, and logistic regression analysis revealed a significant association between AVI and ABPI ≤0.90 (odds ratio = 1.81; 95% confidence interval = 1.15-2.84; p = 0.01). Study 2: In another 19 patients with PAD, percutaneous transluminal angioplasty resulted in a decrease in the AVI from 31 ± 8 to 27 ± 8 ( p < 0.01)., Conclusion: Possible presence of PAD must be taken into account while applying the AVI for the assessment of vascular damage.

Background: Although fractional flow reserve (FFR) measurements during coronary angiography are performed in routine clinical practice, few studies have evaluated FFR measurements in dialysis patients., Methods: We retrospectively studied 42 hemodialysis patients with suspected or known coronary artery disease (CAD) who underwent stress myocardial perfusion imaging and coronary angiography with FFR measurements for 61 coronary lesions. The cut-off value for FFR to detect myocardial ischemia was determined by receiver operating characteristic (ROC) curve analysis., Results: There were 61 coronary vessels measured by FFR. The FFR range was 0.34-0.93 with a mean of 0.74±0.13. The ROC curve analysis revealed that the best cut-off value of FFR for detecting myocardial ischemia was 0.76 (p<0.0001), with 70% sensitivity, 86% specificity, and 76% accuracy for myocardial ischemia. Compared with patients who had positive myocardial ischemia and an FFR≤0.76, those who had negative myocardial ischemia despite an FFR≤0.76 had less left ventricular (LV) mass index, whereas patients who had positive myocardial ischemia despite an FFR>0.76 had greater LV mass indexor serum calcium-phosphorus product., Conclusions: The cut-off value of FFR for myocardial ischemia in chronic hemodialysis patients is similar to that in other CAD patients. However, caution is necessary when FFR measurements are applied to dialysis patients with significantly increased LV mass index or serum calcium-phosphorus product., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The mechanisms underlying the possible contribution of chronic inflammation to the development of hypertension remain unclear. We examined the longitudinal association of inflammation with the progression of vascular and/or renal abnormalities in the development of hypertension., Methods and Results: In 3274 middle-aged Japanese men without hypertension at the study baseline, brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum CRP (C reactive protein) levels were measured annually during a 9-year period. During this study period, 474 participants (14.5%) developed hypertension. Analysis of the repeated-measures data revealed that sustained elevation of serum CRP levels was associated with a longitudinal increase of the brachial-ankle pulse wave velocity. A linear mixed model analysis revealed that higher log-transformed serum CRP values (log CRP) at each measurement were associated with a higher annual increase of the brachial-ankle pulse wave velocity (estimate=32.553±11.635 cm/s per log CRP, P =0.018), and that higher values of the brachial-ankle pulse wave velocity at each measurement were associated with a higher annual elevation of blood pressure (estimate=0.025±0.002 mm Hg per log CRP, P <0.001)., Conclusions: In middle-aged Japanese men without hypertension at study baseline, long-term active inflammation appears to be associated with a longitudinal increase of arterial stiffness. In turn, this longitudinal increase of arterial stiffness appears to be associated with longitudinal elevation of blood pressure to the hypertensive range. Thus, systemic inflammation may play a role in the pathogenesis of hypertension by the progression of arterial stiffness., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging, 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) was approved by the Japanese Ministry of Health, Labour and Welfare in 1992 and has therefore been widely used since in clinical settings. 123 I-MIBG was also later approved by the Food and Drug Administration (FDA) in the United States of America (USA) and it was expected to achieve broad acceptance. In Europe, 123 I-MIBG is currently used only for clinical research. This review article is based on a joint symposium of the Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC), which was held in the annual meeting of JSNC in July 2016. JSNC members and a member of ASNC discussed the standardization of 123 I-MIBG parameters, and clinical aspects of 123 I-MIBG with a view to further promoting 123 I-MIBG imaging in Asia, the USA, Europe, and the rest of the world.

Background: Despite the introduction of the novel cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) in Japan; its diagnostic value in clinical practice remains largely unknown., Methods: The Semiconductor SPECT Study group is a multicenter Japanese registry which registered 1000 patients to evaluate the diagnostic utility of the CZT camera system (Discovery NM530c; GE Healthcare, Haifa, Israel). The patients underwent stress myocardial SPECT and coronary angiography within a 3-month interval. A significant stenosis was defined as ≥75% diameter narrowing based on the American Heart Association classification., Results: Technetium ( 99m Tc) radiotracer (555-1110MBq) was used in 71% and thallium-201 ( 201 Tl) (74-148MBq) in 29%. The scan times with 99m Tc-radiotracer were 5-10min for stress and 3-10min for rest, whereas those with 201 Tl were 5-9min for stress and 8-10min for rest. To detect individual coronary stenosis, the respective sensitivities, specificities, and accuracies were 74%, 85%, and 81% for left anterior descending coronary artery (LAD) stenosis, 76%, 89%, and 85% for left circumflex stenosis, and 72%, 86%, and 82% for right coronary artery stenosis. However, 66% sensitivity and 91% specificity for LAD stenosis were observed with 99m Tc-radiotracer, whereas 88% sensitivity and 63% specificity were found with 201 Tl., Conclusions: The novel CZT SPECT system facilitated a short scan time with reduced radiotracer dose, yielding an acceptable diagnostic performance for angiographical coronary artery disease, although the low sensitivity for LAD detection with 99m Tc-radiotracer needs to be refined., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Although stress single-photon emission computed tomography (SPECT) using a cadmium-zinc-telluride (CZT) camera facilitates radiation dose reduction, only a few studies have evaluated its diagnostic accuracy in Japanese patients by applying fractional flow reserve (FFR) measurements., Methods and results: We prospectively evaluated 102 consecutive patients with suspected or known coronary artery disease with a low-dose stress/rest protocol ((99m)Tc radiotracer 185/370 MBq) using CZT SPECT. Within 3 months, coronary angiography was performed and a significant stenosis was defined as ≥90% diameter narrowing on visual estimation, or as a lesion of <90% and ≥ 50% stenosis with FFR ≤0.80. To detect individual coronary stenosis, the respective sensitivity, specificity, and accuracy were 86%, 75%, and 82% for left anterior descending artery stenosis, 76%, 81%, and 79% for left circumflex artery stenosis, and 87%, 92%, and 90% for right coronary artery stenosis. When limited to 92 intermediate stenotic lesions in which FFR was measured, stress SPECT showed 77% sensitivity, 91% specificity, and 84% accuracy, whereas the diagnostic value decreased to 52% sensitivity, 68% specificity, and 58% accuracy based only on visual estimation of ≥75% diameter narrowing., Conclusions: CZT SPECT demonstrated a good diagnostic yield in detecting hemodynamically significant coronary stenoses as assessed by FFR, even when using a low-dose (99m)Tc protocol with an effective dose ≤5 mSv. (Circ J 2016; 80: 1217-1224).

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., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The detection of significant coronary artery disease (CAD) in patients with heart failure (HF) from left ventricular (LV) systolic dysfunction is crucial. We evaluated the usefulness of LV mechanical dyssynchrony as assessed by phase analysis compared with conventional gated single-photon emission computed tomography to identify ischemic etiology in patients with HF., Methods and Results: Forty-one consecutive patients who were initially admitted to hospital due to HF resulting from systolic dysfunction were evaluated. All patients underwent cardiac catheterization. LV mechanical dyssynchrony was evaluated using SyncTool™ to obtain the phase SD and histogram bandwidth. The changes in phase SD and histogram bandwidth with stress were calculated. The summed stress score, summed difference score, and changes in phase SD and histogram bandwidth with stress were greater in 26 patients with CAD than in 15 patients without CAD (P=0.001 and P=0.01). On multivariate analysis a phase SD of >14° (odds ratio [OR], 16.7) and a summed stress score of >17 (OR, 8.0) best differentiated LV dysfunction of ischemic and non-ischemic etiologies, with a sensitivity of 89% and a specificity of 87% (χ(2)=20), compared with summed stress score only (sensitivity, 46%; specificity, 87%; χ(2)=4.5)., Conclusions: The addition of phase analysis to conventional perfusion analysis enables better differentiation of the etiology of HF in patients with systolic dysfunction.

Background: Although the novel cadmium-zinc-telluride (CZT) camera system provides excellent image quality, its diagnostic value using thallium-201 as assessed on coronary angiography (CAG) and fractional flow reserve (FFR) has not been validated. METHODS AND RESULTS: To evaluate the diagnostic accuracy of the CZT ultrafast camera system (Discovery NM 530c), 95 patients underwent stress thallium-201 single-photon emission computed tomography (SPECT) and then CAG within 3 months. Image acquisition was performed in the supine and prone positions after stress for 5 and 3 min, respectively, and in the supine position at rest for 10 min. Significant stenosis was defined as ≥90% diameter narrowing on visual estimation, or a lesion with <90% and ≥50% stenosis and FFR ≤0.75. To detect individual coronary stenosis, the respective sensitivity, specificity, and accuracy were 90%, 64%, and 78% for left anterior descending coronary artery stenosis, 78%, 84%, and 81% for left circumflex stenosis, and 83%, 47%, and 60% for right coronary artery (RCA) stenosis. The combination of prone and supine imaging had a higher specificity for RCA disease than supine imaging alone (65% vs. 47%), with an improvement in accuracy from 60% to 72%., Conclusions: Using thallium-201 with short acquisition time, combined with prone imaging, CZT SPECT had a high diagnostic yield in detecting significant coronary stenosis as assessed using FFR.

Background: Cadmium-zinc-telluride (CZT) solid-state detectors have been recently introduced into the field of myocardial perfusion imaging. The aim of this study was to prospectively compare the diagnostic performance of the CZT high-speed gamma camera (Discovery NM 530c) with that of the standard 3-head gamma camera in the same group of patients., Methods and Results: The study group consisted of 150 consecutive patients who underwent a 1-day stress-rest (99m)Tc-sestamibi or tetrofosmin imaging protocol. Image acquisition was performed first on a standard gamma camera with a 15-min scan time each for stress and for rest. All scans were immediately repeated on a CZT camera with a 5-min scan time for stress and a 3-min scan time for rest, using list mode. The correlations between the CZT camera and the standard camera for perfusion and function analyses were strong within narrow Bland-Altman limits of agreement. Using list mode analysis, image quality for stress was rated as good or excellent in 97% of the 3-min scans, and in 100% of the ≥4-min scans. For CZT scans at rest, similarly, image quality was rated as good or excellent in 94% of the 1-min scans, and in 100% of the ≥2-min scans., Conclusions: The novel CZT camera provides excellent image quality, which is equivalent to standard myocardial single-photon emission computed tomography, despite a short scan time of less than half of the standard time.

Background: Although the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is used to characterize coronary anatomy based on 9 anatomic criteria such as lesion location and complexity, the relationship between SYNTAX score and myocardial ischemia has yet to be elucidated., Methods and Results: A total of 158 consecutive patients with suspected or known coronary artery disease (CAD), who underwent both (99m)Tc-sestamibi single-photon emission computed tomography (SPECT) and coronary angiography, were evaluated. Stress SPECT was assessed using a 17-segment model, and the percentage of the myocardial defect scores (DS) was calculated. In 37 patients with intermediate-high SYNTAX scores (>22), the number of men and the prevalence of multi-vessel CAD were significantly higher, and the % stress and ischemic DS were significantly greater than in 121 patients with low SYNTAX scores (≤22). Coronary risk factors, however, were similar between the 2 groups. The % stress and ischemic DS significantly correlated with SYNTAX score. In patients with a low SYNTAX score, % stress and ischemic DS also significantly correlated with the SYNTAX score, whereas no such correlation was observed in the intermediate-high SYNTAX score group., Conclusions: SYNTAX score correlated well with myocardial ischemia as assessed on stress SPECT in general. The higher the SYNTAX score, however, the less clear was the correlation with the extent of myocardial ischemia.

Background: Although poststress myocardial stunning is regarded as a marker for severe coronary artery disease (CAD), no study has yet compared the diagnostic value of poststress stunning with transient ischemic dilation (TID) of the left ventricle (LV) for detecting multivessel CAD., Methods and Results: A total of 271 patients with suspected or known CAD underwent adenosine triphosphate (ATP) loading and at-rest gated single-photon emission computed tomography. We assessed myocardial perfusion with a 20-segment model, and analyzed the changes in LV volumetric analysis induced by ATP and an automatically derived TID ratio. In 147 patients with multivessel CAD, the prevalence of multi-territorial ischemia was higher, and the post-ATP increase in end-systolic volume (ESV) and TID ratio were greater, than in the 124 with insignificant or single-vessel CAD (P<0.0001, for all cases). The receiver-operating characteristic curves analysis revealed cutoff values for ESV of 5 ml and a TID ratio of 1.11. Multivariate logistic regression analysis revealed that the combination of a poststress increase in ESV of ≥5 ml and multi-territorial ischemia best identified multivessel CAD, with a sensitivity of 78% and a specificity of 84%, whereas the TID ratio was not shown to be an independent predictor., Conclusions: Post-ATP stress myocardial stunning is superior to the TID ratio for detecting multivessel CAD.

Background: Although stress-induced left ventricular (LV) wall motion abnormality is a well-known marker for extensive coronary artery disease (CAD), no study has yet analyzed whether phase analysis of exercise-induced LV mechanical dyssynchrony may have enhanced diagnostic value over conventional perfusion analysis in the detection of multivessel CAD., Methods and Results: A total of 278 patients with suspected or confirmed CAD underwent both exercise stress (99m)Tc-sestamibi gated single-photon emission computed tomography and coronary angiography. LV mechanical dyssynchrony was evaluated using the SyncTool to obtain the phase SD and histogram bandwidth. In the detection of 128 patients with multivessel CAD, a summed stress score (SSS) of ≥9 showed a sensitivity of 84% and a specificity of 53%, while an increase in phase SD of ≥4.4° and a bandwidth of ≥14° after exercise had sensitivities of 74% and 68%, and specificities of 84% and 91%, respectively. On multivariate analysis the combination of post-stress increases in phase SD, histogram bandwidth, transient ischemic dilation (TID) ratio and SSS best identified multivessel CAD (sensitivity 77%, specificity 88%, χ(2)=181.8), compared with TID ratio and SSS only (sensitivity 70%, specificity 76%, χ(2)=68.9)., Conclusions: The addition of phase analysis to evaluate exercise-induced LV mechanical dyssynchrony on conventional perfusion analysis enabled better identification of patients with multivessel CAD.

Background: Clinical symptoms of coronary artery disease (CAD) are often atypical in women, particularly in those with diabetes mellitus. Therefore, a simple diagnostic test to identify a high-risk subset of women with diabetes who are likely to have CAD is important., Methods and Results: A total of 407 consecutive patients (319 men and 88 women, age range 68 ± 11 years) with suspected CAD, who were not complaining of anginal pain, were evaluated. Among these patients, 170 had diabetes. Stress myocardial perfusion imaging and simultaneous brachial and ankle blood pressure measurements were performed to obtain the ischemic total perfusion deficit (TPD) and ankle-brachial pressure index (ABI), respectively. Ischemic TPD was not significantly different between men and women, whereas ischemic TPD was significantly greater in diabetic patients than in non-diabetic patients (6.9 ± 7.7% vs. 4.9 ± 6.1%; P = 0.005). In diabetic patients, ischemic TPD was not significantly different between men and women. However, women with ABI<0.9 showed significantly greater ischemic TPD than those with ABI≥0.9 (12.1 ± 10.8% vs. 5.1 ± 5.9%; P=0.04), whereas no difference in ABI was observed in men., Conclusions: ABI was useful in evaluating CAD in asymptomatic women with diabetes to detect a high-risk subset showing the ischemic TPD of >10%, which is regarded as a scintigraphic indicator for coronary revascularization.

Iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) imaging is useful to diagnose recent myocardial ischemia. A 27-year-old woman was admitted to our hospital because of aborted cardiac arrest due to ventricular fibrillation. She underwent BMIPP imaging in order to rule out ischemic heart disease. Reduced BMIPP uptake was observed in the inferoseptal segments. Coronary angiography revealed insignificant lesions, and a severe coronary spasm was provoked in the right coronary artery by an intracoronary injection of acetylcholine. The etiology of ventricular fibrillation in this case was considered to be vasospastic angina. The application of BMIPP imaging helped diagnose fatal vasospastic angina in this case.

Objectives: To determine the role of quantitative analysis of poststress and resting left ventricular function using sex-specific criteria to detect high-risk coronary artery disease (CAD) as defined by the Duke CAD Prognostic Index., Methods and Results: Stress technetium-99m-sestamibi-gated single-photon emission computed tomography and coronary angiography were performed in 407 consecutive patients (300 men, 107 women) with suspected CAD. The cut-off point for high-risk CAD was defined as a Duke CAD Prognostic Index of 42. The stress-to-rest ratios of end-diastolic volume (rEDV) and end-systolic volume (rESV) were analyzed. In 102 patients with high-risk CAD, the summed difference scores, rEDV and rESV, were greater than in 305 patients with low-risk to intermediate-risk CAD. The receiver operating characteristic curves revealed that the optimal cut-off points for rEDV and rESV to detect high-risk CAD were 1.10 and 1.11, respectively. Sex-specific rEDV was 1.08 in men, 1.11 in women, and sex-specific rESV was 1.09 in men and 1.20 in women. Multivariate discriminant analysis showed that the combination of sex-specific rEDV, sex-specific rESV, and summed difference scores greater than or equal to 8 best identified high-risk CAD, with a sensitivity of 75% and specificity of 76%., Conclusion: The addition of a sex-specific approach to left ventricular functional analysis using gated single-photon emission computed tomography on conventional perfusion analysis, may help better identify patients with high-risk CAD as defined by the Duke CAD Prognostic Index.

Background: To determine the prognostic value of post-ischemic stunning, the Japanese assessment of cardiac event and survival study by quantitative gated myocardial single-photon emission computed tomography (SPECT) (J-ACCESS) study was reevaluated., Methods and Results: Of the 4,031 patients of the J-ACCESS, the present study evaluated 1,089 who completed gated SPECT both after stress and at rest. To assess post-ischemic stunning, the following measurements (left ventricular volumes after stress minus volumes at rest) were made: Deltaend-systolic volume (DeltaESV), Deltaenddiastolic volume (DeltaEDV) and Deltaejection fraction (DeltaEF). Myocardial stunning defined either as DeltaESV >or=5 ml, DeltaEDV >or=5 ml or DeltaEF or=5 ml or DeltaEDV >or=5 ml than in those without, whereas DeltaEF or=5 ml was also an independent parameter, in addition to LVEF

Background: Although stress-induced myocardial stunning often develops after exercise testing, determinants of this phenomenon have not been evaluated., Methods and Results: Thirty-one patients with 1-vessel coronary artery disease, limited to the left anterior descending artery (LAD), were evaluated by quantitative coronary angiography (QCA) and intracoronary pressure measurements to calculate fractional flow reserve (FFR). In addition, electrocardiogram-gated technetium-99m sestamibi myocardial imaging was acquired >30 min after exercise and 4 h later to assess the development of stunning. Exercise-induced myocardial stunning was observed in 11 patients (35%). In patients with myocardial stunning, a summed stress score (17.3+/-7.1 vs. 8.1+/-6.2, p<0.001), summed difference score (10.3+/-4.1 vs. 2.7+/-1.9, p<0.0001), and wall motion difference score (4.8+/-2.8 vs. 0.9+/-1.1, p<0.0001) were greater than in those without, while diameter stenosis calculated by QCA (55.1+/-17.3% vs. 29.8+/-17.3%, p<0.0001) was greater and FFR reduced significantly (0.54+/-0.13 vs. 0.83+/-0.06, p<0.0001). Of note, 4 out of 21 patients (19%) with <50% LAD stenosis developed myocardial stunning, whereas only one patient with FFR of 0.64 or greater showed stunning. The best cut-off value was determined as 0.64 for FFR and 46% for QCA, providing 91% sensitivity and 100% specificity for FFR (chi-square=57.2), but 91% sensitivity and 80% specificity for diameter stenoses measured by QCA (chi-square=17.8)., Conclusions: The major determinant for exercise-induced myocardial stunning was a severe flow-limiting coronary stenosis, which was more important than anatomical evaluation based on luminal narrowing alone., (Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: Although ischemic electrocardiographic (ECG) changes during dipyridamole or adenosine infusion have been reported as a marker for severe coronary artery disease (CAD), few studies have focused on ST-segment changes with adenosine triphosphate (ATP)-loading myocardial single-photon emission computed tomography (SPECT)., Methods and Subjects: Between January 2003 and August 2008, 4650 consecutive patients underwent ATP-loading SPECT. After 1412 patients with left bundle branch block, pacemaker rhythm, or previous coronary revascularization were excluded, 16 out of 3238 patients (0.5%) showed ischemic ST-segment depression during ATP-loading myocardial SPECT. They were aged 67+/-11 years; 10 were men and 6 women. Of these patients, 8 demonstrated perfusion abnormalities, whereas the remaining 8 showed normal myocardial perfusion imaging. In 6 of the 8 patients with abnormal SPECT, coronary angiography was performed, revealing left main trunk disease in 1 patient, 3-vessel disease in 4, 1-vessel disease with proximal left ascending artery occlusion in 1, and an insignificant lesion in 1. By contrast, no major cardiac event was observed in the 8 patients with normal SPECT during follow-up for an average of 2 years., Conclusion: The prevalence of ischemic ST-segment changes during ATP loading is very rare. However, this finding should be taken into account since almost half of the patients, particularly those with perfusion abnormalities, may have severe CAD which requires coronary revascularization., (Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Although B-type natriuretic peptide (BNP) has emerged as an important predictor for cardiac events, its effect on scintigraphic parameters is unknown., Methods and Results: The Q-PROVE study is a multicenter study to evaluate the prognostic value of ECG-gated SPECT in 175 Japanese elderly patients. In addition, BNP was assessed in 102 patients. Outcome assessment included cardiac events and noncardiac deaths. Twelve elderly patients (12%) had increased BNP >130 pg/ml. The summed stress score (SSS) was greater in patients with increased BNP than in those with normal BNP. Kaplan-Meier survival estimation indicated event-free survival rates at 3 years of 83%, 78%, 88%, 80%, respectively, in patients with BNP >130 pg/ml, SSS >or=7, summed difference score (SDS) >or=2, and dilated end-diastolic volume (EDV), but 98%, 98%, 100%, 94% in those with BNP

Clinical features of ischemic heart disease in the elderly are different from those in non-elderly patients. The prevalence of female patients, hypertension and co-morbidity was higher in the elderly than in non-elderly patients. Atypical clinical presentation should be taken into consideration, particularly in patients with acute coronary syndrome, because early initiation of coronary reperfusion therapy reduces mortality significantly in elderly patients. In chronic stable angina, risk stratification of patients using stress myocardial perfusion imaging plays an important clinical role. The management of coronary risk factors to prevent cardiovascular events is of utmost importance in the elderly since the mortality of acute myocardial infarction is very high. Among classical risk factors, beneficial effects of the management of blood pressure on hypertensive and/or diabetic patients are enormous. Recent development of percutaneous coronary intervention facilitated coronary revascularization to reduce ischemic burden even in patients aged 80 years or older due to the low invasiveness of the procedure. However, cardiac surgery is still regarded as the first option for the elderly ith associated aortic stenosis, diffuse 3-vessel coronary artery disease, or distal left main trunk disease.

Aims: Z-band alternatively spliced PDZ-motif protein (ZASP)/Cypher is a Z-disc component of which several dilated cardiomyopathy (DCM)-associated mutations have been reported. Most of the mutations were found in exons 4 and 10 of ZASP/Cypher gene LDB3 and both exons were expressed preferentially in the heart. The aim of this study was to investigate the functional alteration of ZASP/Cypher caused by the DCM-associated mutations., Methods and Results: The yeast-two-hybrid method was used to identify the protein bound to a domain encoded by exon 4 of LDB3. Interaction of ZASP/Cypher with the binding protein was investigated in relation to the functional alterations caused by LDB3 mutations. Localization of the ZASP/Cypher-binding protein was examined at the cellular level in rat cardiomyocytes. Phosphoglucomutase 1 (PGM1), a metabolic enzyme involved in glycolysis and gluconeogenesis, was identified as a protein interacting with ZASP/Cypher. PGM1 bound to ZASP/Cypher at the domains encoded by exons 4 and 10. Two LDB3 mutations in exon 4 (Ser189Leu and Thr206Ile) and another mutation in exon 10 (Ile345Met) reduced the binding to PGM1. PGM1 showed diffuse localization in the cytoplasm of rat cardiomyocytes under standard culture conditions, and distribution at the Z-discs was observed under stressed culture conditions. Binding of endogenous PGM1 and ZASP/Cypher was found to be enhanced by stress in rat cardiomyocytes., Conclusion: ZASP/Cypher anchors PGM1 to Z-disc under conditions of stress. The impaired binding of PGM1 to ZASP/Cypher might be involved in the pathogenesis of DCM.

Two patients developed bepridil-induced interstitial pneumonia during treatment of arrhythmia. The first patient was a 69-year-old man who received bepridil to maintain sinus rhythm in atrial fibrillation and who developed dyspnea on the 20th day after administration. The second patient was a 72-year-old man who received bepridil for paroxysmal atrial fibrillation and who developed dyspnea on the 60th day after administration. They were diagnosed with interstitial pneumonia on the basis of physical and imaging findings. The first patient was discharged after steroid pulse therapy, and the second patient after improvement of physical and imaging findings when bepridil was discontinued. Although a limited number of cases of bepridil-induced interstitial pneumonia have been reported, the disorder should be kept in mind as an important adverse reaction when breathlessness or dyspnea develops during administration of the drug.

Although the presence of coronary heart disease (CHD) was the major determinant of perioperative mortality and long-term prognosis in patients with aortic aneurysm (AA) and peripheral artery disease (PAD), the prevalence and severity of CHD in patients with individual vascular diseases was unknown. Adenosine triphosphate-loading myocardial single-photon emission computed tomography therefore was performed in 788 patients with vascular diseases of the aorta and peripheral arteries, with AA in 500, PAD localized in the lower-limb arteries in 183, and combined AA and PAD in 105. Patients with known CHD, such as those with previous myocardial infarction or revascularization procedures, were excluded. Myocardial single-photon emission computed tomography was analyzed using a 20-segment model, and summed stress scores and summed difference scores were calculated. Stress-induced myocardial ischemia was defined as a summed difference score >or=2. The presence of myocardial ischemia was highest in patients with combined PAD and AA (73%), followed by PAD (55%; p = 0.005), and the lowest in patients with AA (37%; p <0.0001). Summed stress score was also the highest in patients with combined PAD and AA (11.6 +/- 9.9), followed by PAD (7.8 +/- 8.8; p <0.0001), and the lowest in patients with AA (4.0 +/- 6.2; p <0.0001 for both). Similarly, summed difference score was the highest in patients with combined PAD and AA (6.4 +/- 6.1), followed by PAD (4.4 +/- 5.7; p = 0.001) and AA (2.3 +/- 4.0; p <0.0001 for both). In conclusion, the prevalence of CHD in patients with PAD was >50%, and although myocardial ischemia was observed in only (1/3) of patients with AA, its prevalence not only doubled, but also indicated extensive myocardial ischemia when combined with PAD. Thus, cardiac evaluation was particularly important in patients with combined AA and PAD.

Adenosine is widely used as a pharmacologic agent for stress myocardial perfusion imaging. Vasospasm as a side effect of adenosine has been reported a few times in other countries, but it has not been reported in Japan. A 65-year-old woman was admitted to our hospital because of chest pain at rest and during exercise. She underwent myocardial scintigraphy, to rule out myocardial ischemia. After adenosine infusion, she felt chest pain and the electrocardiogram (ECG) showed ST elevation in inferior leads. Adenosine infusion was stopped immediately. Her chest pain resolved, and the ECG reverted to baseline. Perfusion image presented reverse redistribution in inferior segments, and coronary angiography revealed insignificant lesions. Transient ST elevation during adenosine infusion is thought to be due to coronary vasospasm, judging from scintigraphic and angiographic findings.

Objectives: We sought noninvasively to diagnose left main trunk (LMT) disease using myocardial perfusion imaging (MPI)., Methods: Five 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., Results: In 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., Conclusion: In 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.

Background: Although transient left ventricular (LV) dilation is a well-known marker for extensive coronary artery disease (CAD), few studies performed quantitative analysis of LV function of post adenosine triphosphate (ATP) stress and at rest to detect extensive CAD., Methods: One hundred nineteen patients with suspected CAD underwent post-stress and resting gated single-photon emission computed tomography (SPECT). Myocardial perfusion was assessed with a 20-segment model, and the changes in LV volume and function with ATP were analyzed. In addition, the stress-induced volume ratio (SIVR), defined as stress-to-rest ratios (end-systolic volume x 5 + end-diastolic volume), was calculated. All the patients underwent coronary angiography within 3 months of gated SPECT., Results: In the 62 patients with multi-vessel CAD, the summed stress score (SSS) (16.6 +/- 8.7 vs 11.5 +/- 9.1; P < .002), summed difference score (SDS) (9.6 +/- 5.8 vs 3.9 +/- 4.2; P < .0001), the post-stress increase in end-diastolic volume (EDV) (7.7 +/- 7.9 vs 2.2 +/- 5.3 mL; P < .0001), the post-stress increase in end-systolic volume (ESV) (9.4 +/- 6.0 vs 2.7 +/- 4.0 mL; P < .0001), and the (SIVR) (1.21 +/- 0.14 vs 1.06 +/- 0.10; P < .0001) were greater than in the 57 patients with insignificant or single-vessel CAD, whereas the post-stress increase in ejection fraction (EF) was less (-6.0 +/- 4.9 vs -2.0 +/- 4.4%; P < .0001). In the detection of multi-vessel CAD, an SSS of > or = 14 and an SDS of > or = 9 showed sensitivities of 57% and 52%, respectively, and specificities of 63% and 88%, respectively, while increase in EDV of > or = 6 mL, increase in ESV of > or = 6 mL, decrease in EF of > or = 5% after stress, and SIVR of > or = 1.13 demonstrated sensitivities of 60%, 81%, 60%, and 74% and specificities of 74%, 77%, 77%, and 79%, respectively. The multivariate discriminant analysis revealed that the combination of post-stress increase in ESV and the SDS best identified multi-vessel CAD, with 81% sensitivity and 77% specificity (chi(2) = 63.6), whereas the SDS alone showed 52% sensitivity and 88% specificity (chi(2) = 22.4)., Conclusions: The addition of "post-ATP stress" and "at rest" LV functional analysis using gated SPECT to conventional perfusion analysis helps to better identify patients with multi-vessel CAD.

Objective: Although post-ischemic stunning has emerged as an important marker for severe coronary artery disease (CAD), differences in stress methods may have different effects on left ventricular (LV) volumes and function., Methods: To assess differential effects comparing exercise and pharmacologic stress on the LV measurements, (99m)Tc-sestamibi gated single-photon emission computed tomography (SPECT) acquired more than 30 min after stress and at rest was evaluated in 38 patients undergoing adenosine triphosphate (ATP) stress (ATP group) and 38 age-and sex-matched patients subjected to exercise stress (Ex group) among 268 patients with normal SPECT findings., Results: Coronary risk factors and LV volumetric measurements at baseline were similar in the two groups. Compared with volumetric measurements at rest, end-diastolic volume (EDV) increased (72 +/- 21 ml to 74 +/- 21 ml; P = 0.01), end-systolic volume increased (25 +/- 12 ml to 28 +/- 13 ml; P = 0.001), and ejection fraction (EF) decreased after stress (66% +/- 8% to 63% +/- 9%; P < 0.002) in the ATP group. In the Ex group, by contrast, no such change was observed. In addition, changes in EDV (3 +/- 6 vs. -1 +/- 5 ml; P = 0.01) and the stress-to-rest ratio of EDV (1.04 +/- 0.09 vs. 0.99 +/- 0.08; P < 0.02) after stress were greater in the ATP than in the Ex group., Conclusions: Differential effects of stress methods on LV volumes persist more than 30 min after the stress. These findings should be kept in mind when interpreting post-ischemic stunning.

Objectives: Although the Heston index, derived left ventricular (LV) volumetric analysis, is reported to best represent transient LV dilation on non-gated single-photon emission computed tomography (SPECT), its diagnostic performance has not been proven to identify extensive coronary artery disease (CAD) as assessed by coronary angiogram. Accordingly, we sought to evaluate the diagnostic utility of Heston index to detect multi-vessel CAD., Methods: Post-stress and resting electrocardiogram-gated 99mTc-sestamibi SPECT was performed in 223 patients with suspected or known CAD. All of the patients underwent coronary angiography within 3 months of gated SPECT. The summed stress, summed rest, and summed difference scores were calculated using a 20-segment model. The left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were calculated automatically with the QGS program. In addition, stress-to-rest ratios of EDV, ESV, and (ESVx5+EDV) were calculated; the latter was defined as Heston index., Results: In the 104 patients with multi-vessel CAD, the summed stress score (17.5+/-10.0 vs. 11.7+/-9.2, p<0.001), the summed difference score (9.1+/-6.3 vs. 4.3+/-4.2, p<0.0001), the Heston index (1.17+/-0.15 vs. 1.02+/-0.13, p<0.0001), the stress-to-rest ratio of EDV (1.05+/-0.10 vs. 0.99+/-0.09; p<0.0001), and that of ESV (1.23+/-0.21 vs. 1.04+/-0.17; p<0.0001, respectively) were greater than in the 119 patients with one-vessel CAD or insignificant lesion. The best cut-off value was determined as 1.09 for Heston index, giving a sensitivity of 76%, specificity of 77% for detection of multi-vessel CAD. Multiple stepwise logistic regression analysis showed that Heston index >or =1.09, summed stress score > or =14, and summed difference score > or =9 were the independent predictors of detecting multi-vessel CAD, yielding a sensitivity of 76% and specificity of 77% (global chi 2, 88.8)., Conclusions: The Heston index is simple and achieves higher diagnostic value in the detection of multi-vessel CAD, compared with conventional analysis alone.

Background: Although measuring blood pressure at the bilateral brachia is common in medical practice, its clinical significance in patients with suspected coronary artery disease (CAD) has not been fully clarified., Methods: To define the significance of inter-arm systolic blood pressure difference in patients with suspected CAD, and to assess the relationship between inter-arm pressure difference and CAD, simultaneous brachial and ankle blood pressure measurements and stress myocardial single-photon emission computed tomography (SPECT) were performed in 386 consecutive patients with suspected CAD, excluding those with previous myocardial infarction or coronary revascularization., Results: Subclavian artery stenosis, defined as > or = 15 mmHg inter-arm systolic blood pressure difference, was found in 27 patients (7%). Age (65 +/- 12 vs 65 +/- 11 years), male sex (21/27 vs 244/359), prevalence of hypertension(63% vs 56%), hypercholesterolemia (63% vs 62%), diabetes mellitus(33% vs 38%), cigarette smoking (44% vs 41%) and family history of CAD (15% vs 12%) were similar between patients with subclavian artery stenosis and those without. The incidence of decreased ankle-brachial pressure index (ABI) was higher (37% vs 12%, p = 0.001), and percentage ischemic myocardium as assessed by SPECT was greater (9.0 +/- 8.5% vs 5.6 +/- 6.6%, p < 0.05) in patients with subclavian artery stenosis than in those without. Furthermore, significant correlations were observed between inter-arm pressure difference and percentage ischemic myocardium (r = 0.13; p = 0.01), and ABI (r = -0.26, p < 0.0001). Among 386 patients, 283 underwent coronary angiography, and 63% of those who had inter-arm blood pressure difference had CAD. Furthermore, 83% of those CAD patients had multi-vessel CAD, which is regarded as a high-risk subset for subsequent cardiac events., Conclusions: Inter-arm pressure difference is often found in patients with suspected CAD, and is associated with significant CAD and peripheral artery disease. Thus, inter-arm pressure difference may be regarded as a simple marker for coronary and peripheral artery diseases.

Background: Although electrocardiogram-gated single-photon emission computed tomography (SPECT) may be useful in risk stratification of elderly patients with coronary artery disease (CAD), few studies have prospectively evaluated its prognostic value in this patient population., Methods and Results: A total of 175 patients aged 75 years or more with known or suspected CAD were prospectively evaluated by stress gated SPECT using a 20-segment model and an automatic functional analysis. Patients with acute coronary syndrome within the previous 3 months, and those who underwent coronary revascularization within 3 months after the SPECT study were excluded. Outcome assessment included prespecified cardiac events and noncardiac deaths. During a mean follow-up of 3.4 years, there were 18 cardiac events: 2 cardiac deaths, 1 nonfatal myocardial infarction, 3 coronary artery bypass grafting, 5 percutaneous coronary interventions, 1 unstable angina, 4 heart failures, and 2 malignant arrhythmias. Kaplan-Meier survival estimation indicated an event-free survival rate of 98.1% at 3 years in patients without myocardial ischemia, but 79.9% in those with ischemia as documented by gated SPECT (p=0.0001). Multivariate analysis using the Cox proportional hazard model demonstrated that stress-induced myocardial ischemia was the only independent predictor for subsequent cardiac events (p<0.01)., Conclusions: Stress gated SPECT predicts cardiac events in patients aged 75 years or more with known or suspected CAD and may have a role in risk stratification of this patient population.

Background: Although transient left ventricular (LV) dilation is a well-known marker for extensive coronary artery disease (CAD), few studies have performed quantitative analysis of LV function after stress and at rest to detect extensive CAD., Methods and Results: Poststress and resting gated single photon emission computed tomography (SPECT) was performed in 175 patients with suspected CAD. All of the patients underwent coronary angiography within 3 months of gated SPECT. In the 83 patients with multivessel CAD, the summed difference score was greater (9.2 +/- 7.0 vs 3.3 +/- 4.0, P < .0001), the poststress increase in end-systolic volume (ESV) was larger (7.0 +/- 8.0 mL vs -0.8 +/- 4.7 mL, P < .0001), and the poststress increase in ejection fraction (EF) was less (-4.7% +/- 5.4% vs -0.4% +/- 4.5%, P < .0001) than in the 92 patients with insignificant or single-vessel CAD. In the detection of multivessel CAD, a summed difference score of 9 or greater showed a sensitivity of 46% and specificity of 90%, whereas an increase in ESV of 5 mL or greater and a decrease in EF of 5% or greater after exercise had a sensitivity of 66% and 52%, respectively, and specificity of 87% and 83%, respectively. The multivariate discriminant analysis revealed that the combination of poststress increase in ESV, summed difference score, and diabetes mellitus best identified multivessel CAD, with a sensitivity of 72% and specificity of 84% (chi(2), 81.7)., Conclusions: The addition of poststress and at-rest LV functional analysis by use of gated SPECT to conventional perfusion analysis helps to better identify patients with multivessel CAD.

Mutations in genes for sarcomeric proteins such as titin/connectin are known to cause dilated cardiomyopathy (DCM). However, disease-causing mutations can be identified only in a small proportion of the patients even in the familial cases, suggesting that there remains yet unidentified disease-causing gene(s) for DCM. To explore the novel disease gene for DCM, we examined CRYAB encoding alphaB-crystallin for mutation in the patients with DCM, since alphaB-crystallin was recently reported to associate with the heart-specific N2B domain and adjacent I26/I27 domain of titin/connectin, and we previously reported a N2B mutation, Gln4053ter, in DCM. A missense mutation of CRYAB, Arg157His, was found in a familial DCM patient and the mutation affected the evolutionary conserved amino acid residue among alpha-crystallins. Functional analysis revealed that the mutation decreased the binding to titin/connectin heart-specific N2B domain without affecting distribution of the mutant crystallin protein in cardiomyocytes. In contrast, another CRYAB mutation, Arg120Gly, reported in desmin-related myopathy decreased the binding to both N2B and striated muscle-specific I26/27 domains and showed intracellular aggregates of the mutant protein. These observations suggest that the Arg157His mutation may be involved in the pathogenesis of DCM via impaired accommodation to the heart-specific N2B domain of titin/connectin and its disease-causing mechanism is different from the mutation found in desmin-related myopathy.

Purpose: Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer's disease (AD)., Methods: The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[(123)I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections., Results: Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT., Conclusion: MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.