Recent Advances in Vascular Imaging.

Recent advances in vascular imaging have enabled us to uncover the underlying mechanisms of vascular diseases both ex vivo and in vivo. In the past decade, efforts have been made to establish various methodologies for evaluation of atherosclerotic plaque progression and vascular inflammatory changes in addition to biomarkers and clinical manifestations. Several recent publications in Arteriosclerosis, Thrombosis, and Vascular Biology highlighted the essential roles of in vivo and ex vivo vascular imaging, including magnetic resonance image, computed tomography, positron emission tomography/scintigraphy, ultrasonography, intravascular ultrasound, and most recently, optical coherence tomography, all of which can be used in bench and clinical studies at relative ease. With new methods proposed in several landmark studies, these clinically available imaging modalities will be used in the near future. Moreover, future development of intravascular imaging modalities, such as optical coherence tomography-intravascular ultrasound, optical coherence tomography-near-infrared autofluorescence, polarized-sensitive optical coherence tomography, and micro-optical coherence tomography, are anticipated for better management of patients with cardiovascular disease. In this review article, we will overview recent advances in vascular imaging and ongoing works for future developments.

Marked Impairment of Endothelium-Dependent Digital Vasodilatations in Patients With Microvascular Angina: Evidence for Systemic Small Artery Disease.

OBJECTIVE: It remains to be elucidated whether and how endothelial functions are impaired in peripheral circulation of patients with coronary functional disorders, such as vasospastic angina (VSA) and microvascular angina (MVA). We simultaneously examined endothelial functions of peripheral conduit and resistance arteries in patients with coronary functional disorders, with a special reference to NO and endothelium-dependent hyperpolarization factors. Approach and Results: Based on the results of invasive coronary acetylcholine testing and coronary physiological measurements, we divided 43 patients into 3 groups; VSA, MVA, and VSA+MVA. Endothelium-dependent vasodilatations of the brachial artery and fingertip arterioles to intra-arterial infusion of bradykinin were simultaneously evaluated by ultrasonography and peripheral arterial tonometry, respectively. To assess NO and endothelium-dependent hyperpolarization factors, measurements were repeated after oral aspirin and intra-arterial infusion of NG-monomethyl-L-arginine. Additionally, endothelium-independent vasodilatations to sublingual nitroglycerin and plasma levels of biomarkers for endothelial functions were measured. Surprisingly, digital vasodilatations to bradykinin were almost absent in patients with MVA alone and those with VSA+MVA compared with those with VSA alone. Mechanistically, both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations were markedly impaired in patients with MVA alone. In contrast, endothelium-independent vasodilatations to nitroglycerin were comparable among the 3 groups. Plasma levels of soluble VCAM (vascular cell adhesion molecule)-1 were significantly higher in patients with MVA alone compared with those with VSA alone. CONCLUSIONS: These results provide the first evidence that both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations are markedly impaired in MVA patients, suggesting that MVA is a cardiac manifestation of the systemic small artery disease.

Cardiac Lymphatic Dysfunction Causes Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs In Vivo.

Objective- We have previously demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of coronary vasomotion abnormalities, including drug-eluting stent (DES)-induced coronary hyperconstricting responses. Importantly, the adventitia also harbors lymphatic vessels, which may prevent inflammation by transporting extravasated fluid and inflammatory cells. We thus aimed to examine the roles of coronary adventitial lymphatic vessels in the pathogenesis of DES-induced coronary hyperconstricting responses in a porcine model in vivo. Approach and Results- We performed 2 experimental studies. In protocol 1, 15 pigs were divided into 3 groups with or without DES and with bare metal stent. Nonstented sites 20 mm apart from stent implantation also were examined. In the protocol 2, 12 pigs were divided into 2 groups with or without lymphatic vessels ligation followed by DES implantation at 2 weeks later (n=6 each). We performed coronary angiography 4 weeks after DES implantation, followed by immunohistological analysis. In protocol 1, the number and the caliber of lymphatic vessels were greater at only the DES edges after 4 more weeks. In protocol 2, coronary hyperconstricting responses were further enhanced in the lymphatic vessels ligation group associated with adventitial inflammation, Rho-kinase activation, and less adventitial lymphatic vessels formation. Importantly, there were significant correlations among these inflammation-related changes and enhanced coronary vasoconstricting responses. Conclusions- These results provide evidence that cardiac lymphatic vessel dysfunction plays important roles in the pathogenesis of coronary vasoconstrictive responses in pigs in vivo.

A multicenter trial of extracorporeal cardiac shock wave therapy for refractory angina pectoris: report of the highly advanced medical treatment in Japan.

We have previously demonstrated that cardiac shock wave therapy (CSWT) effectively improves myocardial ischemia through coronary neovascularization both in a porcine model of chronic myocardial ischemia and in patients with refractory angina pectoris (AP). In this study, we further addressed the efficacy and safety of CSWT in a single-arm multicenter study approved as a highly advanced medical treatment by the Japanese Ministry of Health, Labour and Welfare. Fifty patients with refractory AP [mean age 70.9 ± 12.6 (SD) years, M/F 38/12] without the indications of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were enrolled in 4 institutes in Japan. Ischemic myocardial regions in the left ventricle (LV) were identified by drug-induced stress myocardial perfusion imaging (MPI). Shock waves (200 shots/spot at 0.09 mJ/mm2) were applied to 40-60 spots in the ischemic myocardium 3 times in the first week. The patients were followed up for 3 months thereafter. Forty-one patients underwent CSWT and completed the follow-up at 3 months. CSWT markedly improved weekly nitroglycerin use [from 3.5 (IQR 2 to 6) to 0 (IQR 0 to 1)] and the symptoms [Canadian Cardiovascular Society functional class score, from 2 (IQR 2 to 3) to 1 (IQR 1 to 2)] (both P < 0.001). CSWT also significantly improved 6-min walking distance (from 384 ± 91 to 435 ± 122 m, P < 0.05). There were no significant changes in LV ejection fraction evaluated by echocardiography and LV stroke volume evaluated by cardiac magnetic resonance imaging (from 56.3 ± 14.7 to 58.8 ± 12.8%, P = 0.10, and from 52.3 ± 17.4 to 55.6 ± 15.7 mL, P = 0.15, respectively). Percent myocardium ischemia assessed by drug-induced stress MPI tended to be improved only in the treated segments (from 16.0 ± 11.1 to 12.1 ± 16.2%, P = 0.06), although no change was noted in the whole LV. No procedural complications or adverse effects related to the CSWT were noted. These results of the multicenter trial further indicate that CSWT is a useful and safe non-invasive strategy for patients with refractory AP with no options of PCI or CABG.

Prognostic impacts of Rho-kinase activity in circulating leucocytes in patients with vasospastic angina.

Aims: Rho-kinase activity in circulating leucocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). The present study aimed to examine the long-term prognostic impact of Rho-kinase activity in circulating leucocytes in VSA patients. Methods and results: We prospectively enrolled 174 consecutive patients with VSA and 50 non-VSA patients, in whom we measured Rho-kinase activity in circulating leucocytes, and they were followed for a median of 16 months. The primary endpoint was cardiac events including cardiac death, non-fatal myocardial infarction, and hospitalization for unstable angina. During the follow-up period, cardiac events occurred in 10 VSA patients (5.7%) but in none of the non-VSA patients. When we divided VSA patients into two groups by a median value of their Rho-kinase activity, the Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity compared with those with low activity or non-VSA patients (log-rank; P < 0.05, respectively). Receiver-operating characteristic curve analysis showed that Rho-kinase activity value of 1.24 was the best cut-off level to predict cardiac events in VSA patients, and multivariable analysis showed that a value above the cut-off point had the largest hazard ratio to predict poor outcome in VSA patients [hazard ratio (95% confidence interval) 11.19 (1.41-88.95); P = 0.022]. Importantly, combination of the Japanese Coronary Spasm Association risk score and Rho-kinase activity significantly improved the prognostic impact in VSA patients as compared with either alone. Conclusion: Rho-kinase activity in circulating leucocytes is useful for prognostic stratification of VSA patients.

Association of Coronary Perivascular Adipose Tissue Inflammation and Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs: 18F-Fluorodeoxyglucose Positron Emission Tomography Imaging Study.

OBJECTIVE: Although coronary perivascular adipose tissue (PVAT) may play important roles as a source of inflammation, the association of coronary PVAT inflammation and coronary hyperconstricting responses remains to be examined. We addressed this important issue in a porcine model of coronary hyperconstricting responses after drug-eluting stent implantation with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomographic imaging. APPROACH AND RESULTS: An everolimus-eluting stent (EES) was randomly implanted in pigs into the left anterior descending or the left circumflex coronary artery while nonstented coronary artery was used as a control. After 1 month, coronary vasoconstricting responses to intracoronary serotonin (10 and 100 µg/kg) were examined by coronary angiography in vivo, followed by in vivo and ex vivo 18F-FDG positron emission tomographic/computed tomographic imaging. Coronary vasoconstricting responses to serotonin were significantly enhanced at the EES edges compared with the control site (P<0.01; n=40). Notably, in vivo and ex vivo 18F-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced 18F-FDG uptake and its accumulation in PVAT at the EES edges compared with the control site, respectively (both P<0.05). Furthermore, histological and reverse transcription polymerase chain reaction analysis showed that inflammatory changes of coronary PVAT were significantly enhanced at the EES edges compared with the control site (all P<0.01). Importantly, Rho-kinase expressions (ROCK1/ROCK2) and Rho-kinase activity (phosphorylated myosin phosphatase target subunit-1) at the EES edges were significantly enhanced compared with the control site. CONCLUSIONS: These results indicate for the first time that inflammatory changes of coronary PVAT are associated with drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo and that 18F-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.

Renal Denervation Suppresses Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs In Vivo Through the Kidney-Brain-Heart Axis.

OBJECTIVE: Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. APPROACH AND RESULTS: Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation. Drug-eluting stent-induced coronary hyperconstricting responses were significantly enhanced associated with enhanced coronary adventitial SNF and vasa vasorum formation. Protocol 2: pigs implanted with everolimus-eluting stents were randomly assigned to the RDN or sham group. The RDN group underwent renal ablation. At 1 month, RDN significantly caused marked damage of the SNF at the renal arteries without any stenosis, thrombus, or dissections. Notably, RDN significantly upregulated the expression of α2-adrenergic receptor-binding sites in the nucleus tractus solitarius, attenuated muscle sympathetic nerve activity, and decreased systolic blood pressure and plasma renin activity. In addition, RDN attenuated coronary hyperconstricting responses to intracoronary serotonin at the proximal and distal stent edges associated with decreases in SNF and vasa vasorum formation, inflammatory cell infiltration, and Rho-kinase expression/activation. Furthermore, there were significant positive correlations between SNF and vasa vasorum and between SNF and coronary vasoconstricting responses. CONCLUSIONS: These results provide the first evidence that RDN ameliorates drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo through the kidney-brain-heart axis.

Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries.

AIMS: Although the importance of coronary microvascular dysfunction (CMD) has been emerging, reliable biomarkers for CMD remain to be developed. We examined the potential usefulness of plasma concentration of serotonin to diagnose CMD in patients with suspected angina and unobstructive coronary arteries. METHODS AND RESULTS: We enrolled 198 consecutive patients (M/F 116/82, 60.2 ± 13.3 years old) who underwent acetylcholine provocation test and measured plasma serotonin concentration. Coronary microvascular dysfunction was defined as myocardial lactate production without or prior to the occurrence of epicardial coronary spasm during acetylcholine provocation test. Although no statistical difference in plasma concentration of serotonin [median (inter-quartile range) nmol/L] was noted between the vasospastic angina (VSA) and non-VSA groups [6.8 (3.8, 10.9) vs. 5.1 (3.7, 8.4), P = 0.135], it was significantly higher in patients with CMD compared with those without it [7.7 (4.5, 14.2) vs. 5.6 (3.7, 9.3), P = 0.008]. Among the four groups classified according to the presence or absence of VSA and CMD, serotonin concentration was highest in the VSA with CMD group. Importantly, there was a positive correlation between plasma serotonin concentration and baseline thrombolysis in myocardial infarction frame count (P = 0.001), a marker of coronary vascular resistance. The classification and regression trees analysis showed that plasma serotonin concentration of 9.55 nmol/L was the first discriminator to stratify the risk for the presence of CMD. In multivariable analysis, serotonin concentration greater than the cut-off value had the largest odds ratio in the prediction of CMD [odds ratio (95% confidence interval) 2.63 (1.28-5.49), P = 0.009]. CONCLUSIONS: Plasma concentration of serotonin may be a novel biomarker for CMD in patients with angina and unobstructive coronary arteries.

Hip flexor muscle dysfunction during walking at self-selected and fast speed in patients with aortoiliac peripheral arterial disease.

OBJECTIVE: Intermittent claudication aggravates physical function and is associated with an increased risk of death in patients with peripheral arterial disease (PAD). Previous studies on kinetic parameters (joint moment and power) of lower limbs in these patients have largely focused on the decline in the ankle plantar flexor moment and power at self-selected (SS) walking speed, which may not be an optimal condition to induce claudication pain. In the present study, we investigated the abnormalities in joint kinetic parameters in patients with PAD at both SS and at fast walking speeds. METHODS: We recruited 16 patients with aortoiliac PAD (4 unilateral and 12 bilateral) and 10 healthy controls. The participants were instructed to walk at SS and fast speeds along a 7-meter walkway embedded with a force plate. Spatiotemporal parameters and joint kinetic parameters of the lower limbs during the stance phase were recorded using a three-dimensional motion analysis device. RESULTS: Compared with the controls, patients with PAD showed a significant reduction in their walking speed, step length, stride length, and cadence. Further, a reduction in peak hip flexor moment at fast walking speed and in peak hip flexor generation power was observed in both modes of walking. However, no significant between-group differences were observed for the peak ankle plantar flexor moment or power at either walking speed. Multiple regression analysis showed peak hip flexor generation power was a strong contributor to reduction at both SS and fast walking speeds in patients with PAD. CONCLUSIONS: Patients with aortoiliac PAD walk slowly and show reduced kinetic parameters of the hip joint at both SS and fast walking speeds. Our results suggest that hip flexor muscles may be a useful target for exercise training in patients with aortoiliac PAD.

Age-Specific Trends in the Incidence and In-Hospital Mortality of Acute Myocardial Infarction Over 30 Years in Japan　- Report From the Miyagi AMI Registry Study.

BACKGROUND: We are now facing rapid population aging in Japan, which will affect the actual situation of cardiovascular diseases. However, age-specific trends in the incidence and mortality of acute myocardial infarction (AMI) in Japan remain to be elucidated.Methods and Results:We enrolled a total of 27,220 AMI patients (male/female 19,818/7,402) in our Miyagi AMI Registry during the past 30 years. We divided them into 4 age groups (≤59, 60-69, 70-79 and ≥80 years) and examined the temporal trends in the incidence and in-hospital mortality of AMI during 3 decades (1985-1994, 1995-2004 and 2005-2014). Throughout the entire period, the incidence of AMI steadily increased in the younger group (≤59 years in both sexes), while in the elderly groups (≥70 years in both sexes), the incidence significantly decreased during the last decade (all P<0.01). In-hospital cardiac mortality significantly decreased during the first 2 decades in elderly groups of both sexes (all P<0.01), whereas no further improvement was noted in the last decade irrespective of age or sex, despite improved critical care of AMI. CONCLUSIONS: These results provide the novel findings that the incidence of AMI has been increasing in younger populations and decreasing in the elderly, and that improvement in the in-hospital mortality of AMI may have reached a plateau in all age groups in Japan.

European Society of Cardiology (ESC) Annual Congress Report From Barcelona 2017.

From August 26th to 30th, the 2017 Annual Congress of the European Society of Cardiology (ESC 2017) was held in Barcelona, Spain. Despite the terrorism tradegy just before the ESC congress, the congress attracted many medical professionals from all over the world to discuss the recent topics in cardiovascular medicine in more than 500 sessions, including COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS Trial), CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), and ORION (which assessed the effect of a novel siRNA inhibitor to PCSK9 on reductions in low-density lipoprotein cholesterol). Japanese cardiologists and the Japanese Circulation Society greatly contributed to the congress. This report briefly introduces some late-breaking registry results, late-breaking clinical trials, and ESC Guidelines from the ESC 2017 Congress.

Increased Coronary Perivascular Adipose Tissue Volume in Patients With Vasospastic Angina.

BACKGROUND: Recent studies have suggested that coronary perivascular adipose tissue (PVAT) impairs coronary vasomotion, so we examined whether PVAT is increased at the spastic coronary segment in patients with vasospastic angina (VSA). METHODS AND RESULTS: PVAT volume in the left anterior descending (LAD) coronary arteries on CT coronary angiography was significantly increased in 48 VSA patients with LAD spasm compared with 18 controls (30.7±2.0 vs. 21.0±3.2 cm(3), P=0.01), whereas that of total epicardial adipose tissue was comparable between the 2 groups. CONCLUSIONS: The results suggested an important role of PVAT in the pathogenesis of coronary spasm. (Circ J 2016; 80: 1653-1656).

Hippocampal Blood Flow Abnormality Associated With Depressive Symptoms and Cognitive Impairment in Patients With Chronic Heart Failure.

BACKGROUND: Depressive symptoms and memory impairment are prevalent in patients with chronic heart failure (CHF). Although the mechanisms remain to be elucidated, the hippocampus (an important brain area for emotion and memory) may be a possible neural substrate for these symptoms. METHODS AND RESULTS: We prospectively enrolled 40 Stage C patients, who had past or current CHF symptoms, and as controls 40 Stage B patients, who had structural heart disease but had never had CHF symptoms, in Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). As the primary index, we measured cerebral blood flow (CBF) in the 4 anterior-posterior segments of the hippocampus, using brain MRI analysis. Depressive symptoms, immediate memory (IM) and delayed memory (DM) were assessed using Geriatric Depression Scale (GDS), and Wechsler Memory Scale-revised (WMS-R), respectively. Hippocampus CBF in the most posterior segment was significantly lower in Stage C than in Stage B group (P=0.029 adjusted for Holm's method). Multiple regression analysis identified significant association between hippocampus CBF and GDS or DM score in Stage C group (all P<0.05). GDS score was significantly higher, and IM and DM scores were lower in Stage C patients with hippocampus CBF below the median than those with hippocampus CBF above the median (all P<0.05). CONCLUSIONS: Hippocampus abnormalities are associated with depressive symptoms and cognitive impairment in CHF patients. (Circ J 2016; 80: 1773-1780).

Overview of the 80(th) Annual Scientific Meeting of the Japanese Circulation Society　- The Past, Present and Future of Cardiovascular Medicine in Japan -　- The 5(th) Anniversary of the Great East Japan Earthquake.

The 80(th)Annual Scientific Meeting of the Japanese Circulation Society was held in Sendai, Japan, on March 18-20, 2016, which coincided with the 5(th)anniversary of the Great East Japan Earthquake that hit the Tohoku area on March 11, 2011. Thus, the main themes for this meeting were "The Past, Present and Future of Cardiovascular Medicine in Japan" and "The 5(th)Anniversary of the Great East Japan Earthquake". Despite the provincial location, approximately 15,000 people attended during the 3-day meeting, and there were in-depth discussions in each of the various sessions on these themes. Especially, to our great pleasure, the Japanese Royals, Emperor Akihito and Empress Michiko, kindly visited the panel exhibition of the Great East Japan Earthquake and spoke words of appreciation to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates. (Circ J 2016; 80: 1689-1694).

Structural abnormality of the hippocampus associated with depressive symptoms in heart failure rats.

Heart failure (HF) is characterized by a blood supply which is insufficient to meet the body's demand. HF can potentially affect the brain and is associated with a high prevalence of depression. However, the mechanisms by which the two are related remain largely unclear. Structural abnormalities of the ventral hippocampus have been observed in depression but have never been reported in HF. In this study, we thus investigated structural brain abnormality in HF using voxel-based morphometry (VBM) and histological analysis in a rat model of HF. T2-weighted images were obtained in rats with HF (n = 20) and sham rats (n = 17) and VBM was used to produce gray matter concentration (GMC) maps. Twenty-four hour locomotor activity was used as a sign of depressive behavior. Brains of HF and sham rats (n = 8, each) were fixed and histologically analyzed for the measurement of neurogenesis, the number of astrocytes and neurite outgrowth in the ventral hippocampus. VBM demonstrated significant GMC decrease in the hippocampus, which was restricted to the ventral segment. Similarly, neurogenesis and neurite outgrowth were significantly decreased and the number of astrocytes was significantly increased in HF rats as compared with sham rats in the ventral hippocampus. GMC values in the ventral hippocampus were significantly and negatively correlated with 24 hour locomotor activity in HF rats. In conclusion, the present study has demonstrated for the first time that the structural abnormality of the ventral hippocampus is associated with depressive symptoms in HF rats.

Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo.

BACKGROUND: The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined. METHODS AND RESULTS: Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, P<0.01), which was equally prevented by a selective Rho-kinase inhibitor, hydroxyfasudil. A significant difference in vasoconstriction between SES and BES was sustained for 6 months. A micro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges. CONCLUSIONS: The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

Clinical Characteristics of Patients With Acute Myocardial Infarction Who Did Not Undergo Primary Percutaneous Coronary Intervention- Report From the MIYAGI-AMI Registry Study.

BACKGROUND: In the current era of primary percutaneous coronary intervention (PCI), some patients with acute myocardial infarction (AMI) still do not undergo primary PCI. METHODS AND RESULTS: To examine the clinical characteristics of AMI patients who did not undergo primary PCI, we analyzed patients enrolled between 2002 and 2010 in the MIYAGI-AMI Registry Study, in which all AMI patients in the Miyagi prefecture have been prospectively registered. Among a total of 8,640 patients, 1,879 (21.7%) did not undergo primary PCI and their in-hospital mortality was significantly worse compared with those who did (21.4% vs. 6.4%, P<0.01). Multivariate analysis demonstrated that female sex was significantly associated with non-performance of primary PCI [odds ratio (95% confidence interval): 1.40 (1.22-1.61), P<0.001], along with age [1.01 (1.01-1.02), P<0.001] and heart failure on admission [2.69 (2.29-3.16), P<0.001]. When dividing by age, the non-performance rate of primary PCI in females showed a U-shaped prevalence, whereas it simply increased with aging in males. Importantly, female patients aged <80 years had a significantly higher non-performance rate of primary PCI compared with male patients, regardless of the severity of AMI. CONCLUSIONS: These results indicate that in the current PCI era, various factors, including aging, heart failure on admission and sex differences, are associated with non-performance of primary PCI, which remain to be resolved in order to further improve critical care of AMI.

Accuracy of optical frequency domain imaging for evaluation of coronary adventitial vasa vasorum formation after stent implantation in pigs and humans - a validation study - .

BACKGROUND: Coronary adventitia harbors a wide variety of components, such as inflammatory cells and vasa vasorum (VV). Adventitial VV initiates the development of coronary artery diseases as an outside-in supply route of inflammation. We have recently demonstrated that drug-eluting stent implantation causes the enhancement of VV formation, with extending to the stent edges in the porcine coronary arteries, and also that optical frequency domain imaging (OFDI) is capable of visualizing VV in humans in vivo. However, it remains to be fully validated whether OFDI enables the precise measurement of VV formation in pigs and humans. METHODS AND RESULTS: In the pig protocol, a total of 6 bare-metal stents and 12 drug-eluting stents were implanted into the coronary arteries, and at 1 month, the stented coronary arteries were imaged by OFDI ex vivo. OFDI data including the measurement of VV area at the stent edge portions were compared with histological data. There was a significant positive correlation between VV area on OFDI and that on histology (R=0.91, P<0.01). In the human protocol, OFDI enabled the measurement of the VV area at the stent edges after coronary stent implantation in vivo. CONCLUSIONS: These results provide the first direct evidence that OFDI enables the precise measurement of the VV area in coronary arteries after stent implantation in pigs and humans.

Response to Ebola virus disease outbreak in West Africa by the Ministry of Health, Labour and Welfare of Japan in 2014-2015.

Ebola Virus Disease (EVD) is categorized in the Category 1 Infectious Disease under the Act on Infectious Disease Control. Since the Act came into effect in 1999, no confirmed case of viral hemorrhagic fevers (VHF) has been reported, though some clinical samples have been tested for VHF in the National Institute of Infectious Diseases of Japan. Ministry of Health, Labour and Welfare has monitored the situation of the EVD outbreak in West Africa since the first report from Guinea in March 2014 and reinforced quarantine and public health preparedness in August. The whole-of-government response was activated at the end of October, establishing the Ministerial meeting on the Response to the EVD presided by the Prime Minister. The responses have raised the level of preparedness for such a rare import disease like VHF; however elicited many lessons. Even if the current VHF outbreak is over, the risk of the global infectious diseases outbreak will be unchanged. The maintenance and improvement of preparedness and response for infectious diseases emergency such as the Category 1 Infectious Disease outbreak by the improvement of manuals and continuous exercises are crucial for a future domestic response. In addition, human resource development is essential for contributing to global response efforts.

Evidence for brain activation in patients with takotsubo cardiomyopathy.

BACKGROUND: It remains to be elucidated whether brain activity is altered in takotsubo cardiomyopathy. METHODS AND RESULTS: We measured cerebral blood flow (CBF) in 3 consecutive patients with takotsubo cardiomyopathy using (99m)Tc ethyl cysteinate dimmer single photon-emission computed tomography (SPECT) in the acute and chronic phases. In all patients, CBF was significantly increased in the hippocampus, brainstem and basal ganglia and significantly decreased in the prefrontal cortex in the acute phase, which changes subsided in the chronic phase with full recovery of cardiac wall motion. CONCLUSIONS: These results provide the first direct evidence for brain activation in takotsubo cardiomyopathy.