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DOI： 10.1253/circj.CJ-24-0306

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Language：English   Publisher：(一社)日本循環器学会  

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INTRODUCTION: Coronavirus disease 2019 (COVID-19) symptoms are not fully understood in non-hospitalized individuals in Japan, and COVID-19 differentiation by symptoms alone remained challenging. Therefore, this study aimed to examine COVID-19 prediction from symptoms using real-world data in an outpatient fever clinic. METHODS: We compared the symptoms of COVID-19-positive and negative patients who visited the outpatient fever clinic at Imabari City Medical Association General Hospital and tested for COVID-19 from April 2021 to May 2022. This retrospective single-center study enrolled 2,693 consecutive patients. RESULTS: COVID-19-positive patients had a higher frequency of close contact with COVID-19-infected patients compared with COVID-19-negative patients. Moreover, patients with COVID-19 had high-grade fever at the clinic compared with patients without COVID-19. Additionally, the most common symptom in patients with COVID-19 was sore throat (67.3%), followed by cough (62.0%), which was approximately twice as common in patients without COVID-19. COVID-19 was more frequently identified in patients having a fever (≥37.5℃) with a sore throat, a cough, or both. The positive COVID-19 rate reached approximately half (45%) when three symptoms were present. CONCLUSION: These results suggested that COVID-19 prediction by combinations of simple symptoms and close contact with COVID-19-infected patients might be useful and lead to recommendations for testing of COVID-19 in symptomatic individuals.

DOI： 10.7759/cureus.36614

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BACKGROUND: This study evaluated the diagnostic capability of on-site coronary computed tomography-derived computational fractional flow reserve (CT-FFR) determinations for detecting coronary artery disease (CAD), as assessed by invasive fractional flow reserve (FFR).Methods and Results:Seventy-four patients with coronary artery calcium scores <1,500 who underwent coronary CT angiography (CTA) and invasive FFR measurements within 90 days were retrospectively reviewed. CT-FFR was computed using a prototype machine-learning (ML) algorithm in 91 vessels; 47 vessels of 42 patients were determined to have significant CAD (FFR ≤0.8). Correlation between CT-FFR and FFR was good (r=0.786, P<0.001). Per-vessel area under the curve was significantly larger for CT-FFR (0.907, 95% confidence interval: 0.828-0.958) than for CTA stenosis ≥50% (0.595, 0.487-0.697) or ≥70% (0.603, 0.495-0.705) (both P<0.001). Standard coronary CTA classifications recommended further functional tests in 57 patients with moderate or worse stenosis on CTA. CT-FFR analysis (mean analysis time: 16.4±7.5 min) corrected the standard coronary CTA classification in 18 of 74 patients and confirmed it in 45 of 74 patients. Thus, the per-patient diagnostic accuracy of the classifications was improved from 66% (54-77%) to 85% (75-92%). CONCLUSIONS: On-site CT-FFR based on a ML algorithm can provide good diagnostic performance for detecting hemodynamically significant CAD, suggesting the high value of coronary CTA for selected patients in clinical practice.

DOI： 10.1253/circj.CJ-19-0163

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DOI： 10.1093/ehjci/jez131

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BACKGROUND: This study aimed to evaluate the incremental diagnostic value of dynamic myocardial computed tomography (CT) perfusion (CTP) imaging for detecting obstructive coronary artery disease (CAD) in comparison with coronary CT angiography (CTA). METHODS: Thirty-eight patients who had undergone coronary CTA and pharmacological stress dynamic CTP before invasive coronary angiography (ICA) were selected retrospectively. Using ICA, obstructive CAD was defined as the presence of severe (≥70%) or moderate (50-69%) stenosis with fractional flow reserve (FFR) <0.75. For CT evaluations, coronary vessels with any stenosis ≥50%, ≥70% or unassessable lesions were considered significantly stenotic. Dynamic CTP was assessed quantitatively using CT-derived myocardial blood flow (CT-MBF). Receiver operating characteristic (ROC) curve analysis determined the cut-off value of CT-MBF for identifying obstructive CAD. The diagnostic performances of CTA alone and integrated CTA and CTP assessments for detecting obstructive CAD were compared. RESULTS: Using ICA and FFR, 24 of 114 vessels had obstructive CAD. The cut-off value of CT-MBF for detecting obstructive CAD was 1.26mL/g/min. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) at the vessel level were 96%, 57%, 37%, and 98% for CTA, and 83%, 93%, 77%, and 95% for integrated CTA and CTP assessment using cut-off 50% stenosis on CTA, respectively. The sensitivity, specificity, and PPV and NPV at the vessel level were 79%, 69%, 40%, and 93% for CTA, and 71%, 97%, 85%, and 93% for integrated CTA and CTP assessment using cut-off 70% stenosis on CTA, respectively. The area under the ROC curve for CTA and CTP was significantly higher than that for CTA alone (0.96 vs. 0.84, p<0.05). CONCLUSIONS: Stress dynamic myocardial CTP is feasible to detect hemodynamically obstructive CAD in patients with high pre-test likelihood and helps for improving diagnostic performance in comparison with coronary CTA alone.

DOI： 10.1016/j.jjcc.2018.12.006

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DOI： 10.1016/j.clinimag.2019.03.016

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Language：English  

DOI： 10.1253/circj.CJ-18-1039

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1253/circj.CJ-18-0047

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.eclinm.2018.09.006

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Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration.

DOI： 10.1242/bio.034009

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PURPOSE: Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients. METHODS: Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole. RESULTS: Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain <20.3% than with active strain ≥20.3% (P = .01). CONCLUSION: Loss of LA active function was associated with increased cardiac events in patients with HCM.

DOI： 10.1111/echo.13886

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science  

The Morris water maze test (MWM) is a useful tool to evaluate rodents’ spatial learning and memory, but the outcome is susceptible to various experimental conditions. Thigmotaxis is a commonly observed behavioral pattern which is thought to be related to anxiety or fear. This behavior is associated with prolonged escape latency, but the impact of its frequency in the early stage on the final outcome is not clearly understood. We analyzed swim path trajectories in male C57BL/6 mice with or without bilateral common carotid artery stenosis (BCAS) treatment. There was no significant difference in the frequencies of particular types of trajectories according to ischemic brain surgery. The mouse groups with thigmotaxis showed significantly prolonged escape latency and lower cognitive score on day 5 compared to those without thigmotaxis. As the next step, we made a convolutional neural network (CNN) model to recognize the swim path trajectories. Our model could distinguish thigmotaxis from other trajectories with 96% accuracy and specificity as high as 0.98. These results suggest that thigmotaxis in the early training stage is a predictive factor for impaired performance in MWM, and machine learning can detect such behavior easily and automatically.

DOI： 10.1371/journal.pone.0197003

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© 2018, International Heart Journal Association. All rights reserved. The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM. Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

DOI： 10.1536/ihj.17-377

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12574-017-0348-2

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BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

DOI： 10.1253/circj.CJ-17-1042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)  

Background The Shikoku Rivaroxaban Registry Trial (SRRT) is a retrospective survey of the use of rivaroxaban for stroke prevention in elderly patients in Shikoku, Japan. Methods The SRRT enrolled 1339 patients from 8 hospitals. Patients were divided into two groups according to their age, the extreme elderly group (453 patients aged ≧80 years) and the control group (886 patients aged &lt
80 years). Results In the extreme elderly group, 41.5% of the patients had low body weight (&lt
50 kg) and 65.1% had abnormal renal function (creatinine clearance &lt
50 ml/min). The mean CHADS2, CHA2DS2-VASc, and HAS BLED scores were 2.7, 4.4, and 2.3, respectively. There were 333 (73.5%) patients who met the dosing criteria, and of these patients, 81.2% received rivaroxaban 10 mg daily. Thromboembolic events occurred in 4 patients (0.94%/person year) and intracranial hemorrhage occurred in 4 patients (0.89%/person year). The incidence of these events was not significantly different from the control group. In addition, all patients with cerebral infarction had been treated with a smaller dose of rivaroxaban than recommended by the dosing criteria, suggesting that dosing criteria should be adhered to. Conclusion These results suggest that rivaroxaban is effective and safe in extreme elderly patients with atrial fibrillation.

DOI： 10.1016/j.jjcc.2017.08.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Heart Association Inc.  

Background--The classical renin-angiotensin system is known as the angiotensin (Ang)-converting enzyme/Ang II/Ang type 1 receptor axis, which induces various organ damage including cognitive decline. The angiotensin-converting enzyme 2/Ang-(1-7)/ Mas axis is known to exert antagonistic actions against the classical renin-angiotensin system axis in the cardiovascular system. However, its roles in the brain remain unclear. We examined possible roles of the angiotensin-converting enzyme 2/Ang-(1-7)/Mas axis in cognitive function, employing vascular cognitive impairment model mice. Methods and Results--Male 10-week-old C57BL6 (wild-type mice, Mas1 knockout mice, Ang II type 2 receptor knockout mice, and Ang II type 2 receptor/Mas1 double knockout mice were subjected to bilateral carotid artery stenosis (BCAS) surgery. Six weeks after treatment, they were subjected to cognitive tasks. Brain samples were used for histopathological analysis. Cognitive function was significantly impaired in wild-type and double knockout mice after BCAS. On the other hand, the cognitive function of Mas1 knockout mice was maintained in spite of the reduction of cerebral blood flow with BCAS. Total cell number in the dentate gyrus region was significantly reduced after BCAS in wild-type but not in Mas1 knockout mice. The number of doublecortin-positive cells in the subgranular zone was not significantly different between wild-type and Mas1 knockout mice. Ang-(1-7) administration did not improve cognitive function in all mice after BCAS surgery. Conclusions--Lack of the Mas receptor may have a protective effect against chronic brain ischemia when the Ang II type 2 receptor exists.

DOI： 10.1161/JAHA.117.008121

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science  

The Morris water maze test (MWM) is one of the most popular and established behavioral tests to evaluate rodents’ spatial learning ability. The conventional training period is around 5 days, but there is no clear evidence or guidelines about the appropriate duration. In many cases, the final outcome of the MWM seems predicable from previous data and their trend. So, we assumed that if we can predict the final result with high accuracy, the experimental period could be shortened and the burden on testers reduced. An artificial neural network (ANN) is a useful modeling method for datasets that enables us to obtain an accurate mathematical model. Therefore, we constructed an ANN system to estimate the final outcome in MWM from the previously obtained 4 days of data in both normal mice and vascular dementia model mice. Ten-week-old male C57B1/6 mice (wild type, WT) were subjected to bilateral common carotid artery stenosis (WT-BCAS) or sham-operation (WT-sham). At 6 weeks after surgery, we evaluated their cognitive function with MWM. Mean escape latency was significantly longer in WT-BCAS than in WT-sham. All data were collected and used as training data and test data for the ANN system. We defined a multiple layer perceptron (MLP) as a prediction model using an open source framework for deep learning, Chainer. After a certain number of updates, we compared the predicted values and actual measured values with test data. A significant correlation coefficient was derived form the updated ANN model in both WT-sham and WT-BCAS. Next, we analyzed the predictive capability of human testers with the same datasets. There was no significant difference in the prediction accuracy between human testers and ANN models in both WT-sham and WT-BCAS. In conclusion, deep learning method with ANN could predict the final outcome in MWM from 4 days of data with high predictive accuracy in a vascular dementia model.

DOI： 10.1371/journal.pone.0191708

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DOI： 10.1002/ehf2.12190

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Optical coherence tomography (OCT) provides accurate visualization of coronary artery morphology. The aim of this study was to investigate the relation between FFR and OCT-derived FFR. We retrospectively analyzed 31 lesions (25 left anterior descending arteries, 2 left circumflex arteries, and 4 right coronary arteries) in 31 patients with moderate-to severe coronary stenosis, who underwent OCT and FFR measurements simultaneously. OCT-derived FFR was calculated by the original algorithm, which was calculated using the following equation based on fluid dynamics: Delta P = FV + SV2, where V is the flow velocity, F is the coefficient of pressure loss because of viscous friction (Poiseuille resistance), and S is the coefficient of local pressure loss because of abrupt enhancement (flow separation). Mean values of % diameter stenosis by quantitative coronary angiography and FFR were 55.2 +/- 14.0% and 0.70 +/- 0.14, respectively. OCT-derived FFR showed a stronger linear correlation with FFR measurements (r = 0.89, p &lt;0.001; root mean square error = 0.062 FFR units) than quantitative coronary angiography % diameter stenosis (r = 0.65, p &lt;0.001), OCT measurements of minimum lumen area (r = 0.68, p &lt;0.001), and % area stenosis (r = 0.70, p &lt;0.001). OCT-derived FFR has the potential to become an alternative method for the assessment of functional myocardial ischemia, and may elucidate the relation between coronary morphology and FFR. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2017.07.083

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: Quantitative assessment of myocardial flow reserve (MFR) by single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is challenging but may facilitate evaluation of multi-vessel coronary artery disease (CAD).
Methods: We enrolled 153 patients with suspected or known CAD, referred for pharmacological stress MPI. They underwent a Tc-99m-perfusion stress/rest SPECT with an ultrafast cadmium-zinc-telluride (CZT) camera. Dynamic data were acquired and time-activity curves fitted to a 1-tissue compartment analysis with input function. K1 was assigned for stress and rest data. The MFR index (MFRi) was calculated as K1 stress/K1 at-rest. The findings were validated by invasive coronary angiography in 69 consecutive patients.
Results: The global MFRi was 1.46 (1.16-1.76), 1.33 (1.12-1.54), and 1.18 (1.01-1.35), for 1-vessel disease (VD), 2-VD, and 3-VD, respectively. In the 3-VD, global MFRi was lower than that in 0-VD (1.63 [1.22-2.04], P &lt; 0.0001) and 1-VD (P = 0.003). Multivariate logistic regression analysis for 3-VD showed significant associations with smoking history (odds ratio [OR]: 4.4 [0.4-8.4]), left ventricular ejection fraction (OR: 61.6 [57.5-66.0]), and global MFRi (OR: 119.6 [111.5-127.7], P = 0.002). A cut-off value of 1.3 yielded 93.3% sensitivity and 75.9% specificity for diagnosing 3-VD. Fractional flow reserve positively correlated with regional MFRi (r = 0.62, P = 0.008), and the SYNTAX score correlated negatively with global MFRi (r = 0.567, P = 0.0003).
Conclusion: We developed and validated a clinically available method for MFR quantification by dynamic Tc-99m-perfusion SPECT utilizing a CZT camera, which improves the detectability of multi-vessel CAD. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ijcard.2017.06.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Perivascular adipose tissue exhibits characteristics of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of obesity/metabolic syndrome. However, the precise role of perivascular adipose tissue in the progression of abdominal aortic aneurysm remains unclear. To test the hypothesis that genetic deletion of angiotensin II type 1a (AT(1a)) receptor in perivascular visceral adipose tissue (VAT) can attenuate aortic aneurysm formation in apolipoprotein E-deficient (ApoE(-/-)) mice, we performed adipose tissue transplantation experiments by using an angiotensin II-induced aneurysm murine model, in which we transplanted VAT from ApoE(-/-) or ApoE(-/-) AT(1a)(-/-) donor mice onto the abdominal aorta of ApoE(-/-) recipient mice. Compared with ApoE-/VAT transplantation, ApoE(-/-)AT(1a)(-/-) VAT transplantation markedly attenuated aortic aneurysm formation, macrophage infiltration, and gelatinolytic activity in the abdominal aorta. AT(1a) receptor activation led to the polarization of macrophages in perivascular VAT toward the proinflammatory phenotype. Moreover, osteopontin expression and gelatinolytic activity were considerably lower in ApoE(-/-)AT(1a)(-/-) perivascular VAT than in ApoE(-/-) perivascular VAT, and angiotensin II-induced osteopontin secretion from adipocytes was eliminated after deletion of AT(1a) receptor in adipocytes. Notably, induction of macrophage migration by conditioned medium from angiotensin II-stimulated wild-type adipocytes was suppressed by treatment with an osteopontin-neutralizing antibody, and ApoE(-/-) OPN-/- VAT transplantation more potently attenuated aortic aneurysm formation than ApoE(-/-) VAT transplantation. Our findings indicate a previously unrecognized effect of AT(1a) receptor in perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

DOI： 10.1161/HYPERTENSIONAHA.117.09512

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Paradoxical low-flow, low-gradient aortic stenosis (LFLG AS) is recognized as a subtype of aortic stenosis. A small left ventricular (LV) cavity with marked LV concentric remodeling leads to a reduced stroke volume in this condition. The case is reported of a paradoxical LFLG AS patient who was undergoing treatment for pulmonary hypertension (PH) and interstitial pneumonia associated with scleroderma. Echocardiography demonstrated enlargement of the right ventricle and a diminished LV cavity. Moreover, the aortic valve opening was restricted despite a preserved LV ejection fraction (61%). The patient's aortic valve area (obtained with the continuity equation) was 0.57 cm2 (indexed AVA was 0.39 cm2/m2), and the mean gradient was 16 mmHg. Multi-detector computed tomography findings confirmed that the aortic valve calcification was not severe. The main mechanism responsible for LFLG AS was considered to be a reduced LV cavity secondary to PH, rather than a sclerotic aortic valve. Thus, a decision was taken to treat the patient with additional medical management prior to performing any invasive procedures. It should be borne in mind that PH can lead to paradoxical LFLG AS, and that appropriate treatment should be contemplated depending on the underlying mechanisms. Video 1: Transthoracic echocardiography in the parasternal long-axis view showing right ventricular dilatation and a diminished left ventricular cavity. Video 2: Transthoracic echocardiography in the shortaxis view showing enlargement of the right ventricle and septal flattening due to pulmonary hypertension. Video 3: Transesophageal echocardiography clearly demonstrates an insufficient valve opening.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).
This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure.
The age, ratio of males, and HbA(1)C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints.
Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT.

DOI： 10.1007/s10557-017-6740-3

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Language：English   Publisher：JAPANESE CIRCULATION SOC  

DOI： 10.1253/circj.CJ-16-0945

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Language：English   Publisher：OXFORD UNIV PRESS  

DOI： 10.1093/eurheartj/ehx125

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DOI： 10.1016/j.hrcr.2017.02.001

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1161/CIRCINTERVENTIONS.116.004692

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: To examinewhether the use of one value of natriuretic peptides to define " normal" is appropriate in all individuals, and to assess the influence of sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP) levels.
Methods and results: A total of 1375 apparently healthy people (women: 155, men: 1220), aged 18-70 yearswere enrolled. Both ANP and BNP levels were higher in women than in men (ANP: 12.50 +/- 6.82 pg/mL vs 8.18 +/- 4.19 pg/mL; BNP: 9.85 +/- 7.63 pg/mL vs 7.03 +/- 6.97 pg/mL). The subjects were divided into three age groups: group I, 18-30 years; group II, 30-50 years; group III, 50-70 years. First, the influence of age on ANP and BNP levels was examined. In women, both ANP and BNP levels were higher in groups II and III than those in group I. In men, ANP and BNP levels increased with age. Second, sex differences in ANP and BNP levels due to age were examined. ANP level was higher in women than that in men in all age groups. BNP level was higher in women than that in men in groups I and II. Multivariate analysis indicated that both ANP and BNP levels were influenced by age, hemoglobin level, and platelet counts.
Conclusion: Because ANP and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin levels, the use of a single value to define " normal" in all individuals is not appropriate. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2016.11.197

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Objective: The clinical significance of atrial high-rate episodes (AHREs) detected by cardiac devices among patients with implantable pacemakers has recently emerged. However, the relationship between AHREs and ischaemic stroke and systemic embolism (SE) is not well understood in the Japanese population. Methods: This study included 343 patients with pacemakers capable of continuous atrial rhythm monitoring (167 males; mean age, 80±7 years). Atrial tachyarrhythmia detection was programmed to the nominal setting of each device, and AHRE was defined as any episode of sustained atrial tachyarrhythmia lasting for more than 6 min. Thromboembolic risk was defined based on the CHADS2 score. Results: During the follow-up period (52±30 months), 165 (48%) patients had at least one episode of AHREs, and 19 (6%) patients experienced stroke/SE. Among patients who experienced stroke/SE, 14 had AHREs before the stroke/SE. AHREs were significantly associated with stroke/SE (HR 2.87; 95% CI 1.10 to 8.90; p=0.03). Subgroup analysis conducted to investigate the impact of the CHADS2 score severity on stroke/SE revealed that AHREs were not associated with stroke/SE in patients with low or intermediate thromboembolic risk (CHADS2 score 0-2; n=217). In contrast, among patients with high thromboembolic risk (CHADS2 score>2; n=126), there was a significant association between AHREs and the incidence of stroke/SE (HR 3.73; 95% CI 1.06 to 13.1; p=0.04). Conclusion: AHREs detected by pacemaker were associated with ischaemic stroke/SE in the Japanese population. However, this association was observed only in the high thromboembolic risk group.

DOI： 10.1136/heartasia-2017-010954

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

A 44-year-old man was implanted with a sirolimus-eluting stent in the proximal left anterior descending artery 8 years previously. Six years later, multi-slice computed tomography and angiography confirmed the formation of a coronary artery aneurysm around the stent. Optical coherence tomography revealed organized thrombi within the stent. Eight years after implantation, the patient presented with chest pain, and multiple imaging modalities revealed thrombotic occlusion within the stent. Surprisingly, the coronary artery aneurysm became a detour for distal flow from the occluded stent. Long-term follow-up after implantation of first-generation drug-eluting stents is mandatory, because unexpected reactions can suddenly occur. &lt
Learning objective: The present case experienced two episodes of unstable angina in very late stage after sirolimus-eluting stent implantation. In addition to the chronic inflammatory reactions and progressive positive remodeling, turbulent and sluggish blood flow within the aneurysm may have resulted in the stagnation of coronary flow, leading to multiple episodes of very late stent thrombosis. Careful and long-term follow-up using multiple imaging modalities should be mandatory after the first drug-eluting stent implantation.&gt

DOI： 10.1016/j.jccase.2016.08.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ Publishing Group  

Objectives Readmission is a common and serious problem associated with heart failure (HF). Unfortunately, conventional risk models have limited predictive value for predicting readmission. The recipients of long-term care insurance (LTCI) are frail and have mental and physical impairments. We hypothesised that adjustment of the conventional risk score with an LTCI certificate enables a more accurate appreciation of readmission for HF. Methods We investigated 452 patients with HF who were followed up for 1 year to determine all-cause readmission. We obtained their clinical and socioeconomic data, including LTCI. The three clinical risk scores used in our evaluation were Keenan (2008), Krumholz (2000) and Charlson (1994). We used net reclassification improvement (NRI) to assess the incremental benefit. Results Patients with LTCI were significantly older, and had a higher prevalence of cerebrovascular disease and dementia than those without LTCI. One-year all-cause readmission (n=193, 43%) was significantly associated with all risk scores, receiving LTCI and the category of LTCI. Receiving LTCI was associated with readmission independent of all risk scores (HR, 1.59 to 1.63
all p&lt
0.01). Adding LTCI to all risk scores led to a significantly improved reclassification, which was observed in the subgroup of patients with HF with preserved ejection fraction (≥50%) but not in the subgroup with reduced ejection fraction (&lt
50%). Conclusions Possession of an LTCI certificate was independently associated with 1-year all-cause readmission after adjusting for validated clinical risk scores in patients with HF. Adding LTCI status significantly improved the model performance for readmission risk, particularly in patients with HF and preserved ejection fraction.

DOI： 10.1136/openhrt-2016-000501

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DOI： 10.1016/j.ijcard.2016.08.248

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AHI measured using type-3 PM is a useful predictor of outcome following initial PVI in patients with paroxysmal AF.

DOI： 10.1007/s10840-016-0148-z

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DOI： 10.1016/j.ijcard.2016.06.278

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. However, it has the disadvantage of cost and invasive complication risks. We investigated the usefulness of quantitative coronary angiography derived translesional pressure (QCA-TP) for predicting functional myocardial ischemia, using FFR as the gold standard. We retrospectively analyzed 152 coronary narrowings (98 left anterior descending arteries, 28 left circumflex arteries, and 26 right) in 132 patients with mild-severe coronary stenosis who underwent coronary angiography and FFR measurements simultaneously. QCA-TP was calculated using software implemented in the QCA software. Coronary morphology was calculated using both densitometry and lumen edges. Functional myocardial ischemia was defined as an FFR of 0.8 or less. The mean values of diameter stenosis by QCA and FFR were 48.9% +/- 14.9 and 0.76 +/- 0.14, respectively. QCA-TP was significantly correlated with FFR (r = 0.76, p &lt;0.01). The cut-off values of QCA-TP for predicting functional myocardial ischemia based on FFR were 72.8 mm Hg for the left, anterior descending arteries (accuracy, 86.7%; area under the curve [AUC], 0.93), 60.5 mm Hg for the left circumflex arteries (accuracy, 89.3%; AUC, 0.88), and 64.4 mm Hg for the right (accuracy, 88.5%; AUC, 0.94). Therefore, our data suggest that QCA-TP can predict myocardial ischemia with high diagnostic accuracy. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2016.07.026

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Takotsubo cardiomyopathy is a cardiac syndrome characterized by reversible left ventricular wall motion abnormalities. It mimics the acute coronary syndrome
however, significant obstructive coronary artery disease is absent. The prognosis is relatively favorable in many cases, but complications may occur during the acute stage. Herein, we present a case of takotsubo cardiomyopathy in a 76-year-old woman. Three days after admission for persistent chest pains, the patient suddenly developed right hemiplegia, right homonymous hemianopsia, and aphasia. By diffusion-weighted magnetic resonance imaging and magnetic resonance angiography, we diagnosed acute-phase cerebral infarction caused by abrupt occlusion of the left middle cerebral artery by a thrombus, and treated it with intravenously administered tissue plasminogen activator. Three hours afterward, the patient's condition improved considerably. She was discharged 15 days after admission without any neurological sequelae. Thus, we show that takotsubo cardiomyopathy complicated by cerebral emboli can be successfully treated using tissue plasminogen activator.&lt
Learning objective: Serious complications sometimes occur during the acute stage of takotsubo cardiomyopathy. Cerebral thromboembolisms are relatively common complications of takotsubo cardiomyopathy that require careful observation during acute phase, and anticoagulant therapy needs to be considered. In case of cerebral emboli, rapid treatment by tissue plasminogen activator infusion may lead to a favorable prognosis.&gt
.

DOI： 10.1016/j.jccase.2015.12.005

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Language：English   Publisher：OXFORD UNIV PRESS  

DOI： 10.1093/eurheartj/ehv604

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Background: Cibenzoline, a class Ia antiarrhythmic drug, is useful for reducing the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, chronic effects of cibenzoline on LVPG and left ventricular (LV) remodeling are unknown.
Methods: Forty-one patients with HOCM participated in this study. Echocardiographic, electrocardiographic, and brain natriuretic peptide (BNP) data collected before and after cibenzoline treatment were compared. From the relation between LVPG and plasma concentration of cibenzoline, an efficacious plasma concentration of cibenzoline was estimated.
Results: The mean follow-up period was 74.2 +/- 47.1 months. The LVPG decreased from 104.8 +/- 62.6 mmHg to 27.6 +/- 30.5 mmHg (p &lt; 0.0001). The LV end-diastolic dimension increased from 42.8 +/- 5.8 mm to 46.2 +/- 5.4 mm (p &lt; 0.0001), but neither LV end-systolic dimension nor LV fractional shortening changed significantly. The left atrial dimension decreased from 40.0 +/- 4.7 mm to 36.2 +/- 5.1 mm (p &lt; 0.0001). The E-wave velocity/A-wave velocity ratio increased, early diastolic annular velocity (Ea) increased, and E/Ea ratio decreased. The interventricular septal wall thickness, LV posterior wall thickness, the Sokolow-Lyon index, and the depth of negative T wave decreased. The heart rate-corrected QT interval was shortened. Plasma BNP level decreased from 418.8 +/- 423.7 pg/ml to 213.7 +/- 154.1 pg/ml(p &lt; 0.02). The safe and efficacious plasma concentration of cibenzoline was between 300 ng/mL and 1500 ng/mL.
Conclusions: Long-term treatment with cibenzoline attenuated LVPG, improved LV diastolic dysfunction, and induced LV hypertrophy regression in patients with HOCM without causing serious complications. (C) 2015 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

DOI： 10.1016/j.jjcc.2015.05.014

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Intraprocedural stent thrombosis (IPST) is a rare complication of percutaneous coronary intervention that leads to poor outcomes; however, the factors contributing to IPST remain largely unknown. Accordingly, we used intravascular ultrasound (IVUS) to examine the lesion characteristics in patients with IPST. We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients (326 with ST-segment elevation myocardial infarction [STEMI], 403 patients with non ST-segment elevation acute coronary syndrome [NSTE-ACS], and 595 patients with stable angina). Of these, IPST occurred in 5 patients during percutaneous coronary intervention (0.4% per patient; 3 with STEMI, 2 with NSTE-ACS). The IVUS characteristics of plaques that developed IPST were compared with those of controls without the evidence of IPST (non-IPST; n = 15) who were matched by age, gender, lesion location, and clinical presentation (STEMI, NSTE-ACS, or stable angina). All 5 lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. Plaque rupture was also observed in 40% of the non-IPST group. Multiple plaque ruptures in the culprit lesion were more common in the IPST group (80% vs 7%; p &lt;0.01). The maximum cavity area was larger in the IPST group than in the non-IPST group having plaque rupture (4.6 mm(2) [inter quartile range, 4.3 to 6.5] vs 2.4 mm(2) [1.8 to 2.9]; p &lt;0.01). In conclusion, we found using IVUS that multiple plaque ruptures with larger cavities more often evolved into IPST. (c) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2015.12.026

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling.
Methods and Results: Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB &gt;= 2.5%, n=33) and group L (CK-MB &lt;2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P&lt;0.0001), fractional shortening decreased (P&lt;0.0004), and left atrial dimension increased (P&lt;0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P&lt;0.02) and left atrial dimension increased (P&lt;0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H.
Conclusions: Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF.

DOI： 10.1253/circj.CJ-15-0872

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This study investigated the relationship between the degree of atherosclerotic changes in the descending thoracic aorta (TA) and the coronary artery using angioscopy. Twenty-five consecutive patients undergoing angioscopy of the TA and coronary angiography were enrolled in this study. Participants were divided into three groups according to the angioscopic grading of the TA: white plaque group (W-group), yellow plaque group (Y-group) and intensive yellow, ruptured plaque with ulceration and/or thrombus group (RP-group). The maximum plaque grade, plaque score, number of yellow plaques, frequency of yellow-plaque grades by coronary angioscopy, and SYNTAX score by coronary angiography were evaluated. Brachial-artery pulse wave velocity and high-sensitivity C-reactive protein level tended to be higher in the RP-group than in the other groups, although the differences were not statistically significant. The SYNTAX score was significantly higher in the RP-group than in the W-group (W-group 4.0 +/- A 3.6 vs. RP-group 17.5 +/- A 10.0, P = 0.045). In addition, the angioscopic maximum plaque grade, plaque score, and number of yellow plaques in the RP-group were significantly higher than in the W-group (maximum plaque grade W-group 0.8 +/- A 0.4 vs. RP-group 1.8 +/- A 0.8, P = 0.026; plaque score W-group 1.0 +/- A 1.2 vs. RP-group 4.0 +/- A 1.4, P = 0.014; and number of yellow plaques W-group 1.0 +/- A 1.2 vs. RP-group 2.5 +/- A 0.5, P = 0.023). The yellow-plaque grade in the coronary artery was correlated significantly with the plaque grading of TA (P = 0.043). Our study suggests that the angioscopic progression of aortic atherosclerosis is closely associated with vulnerability to and the extent of coronary stenosis, indicating that vulnerability toward atherosclerotic plaque development occurs simultaneously in the coronary tree and systemic arteries.

DOI： 10.1007/s10554-015-0669-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

An 84-year-old woman was urgently referred to our hospital owing to persistent malaise and chest pain. Takotsubo cardiomyopathy was diagnosed following transthoracic echocardiography, emergency coronary angiography, and left ventriculography. A left ventricular pressure tracing during cardiac catheterization revealed a 72. mmHg-intraventricular pressure gradient (LVPG). Although β-blockers are effective at reducing LVPG in takotsubo cardiomyopathy, such treatment was contraindicated in our patient owing to her history of bronchial asthma. Therefore, we administered intravenous cibenzoline succinate to attenuate her LVPG. The LVPG decreased to 18. mmHg within 10. min after intravenous cibenzoline succinate administration. During her subsequent hospitalization, the patient showed excellent functional recovery, without any complications. Left ventriculography, performed 21 days after admission, showed normal wall motion and a left ventricular ejection fraction of 68%.&lt
. Learning objective: The prognosis of takotsubo cardiomyopathy is generally good, however, fatal complications have been reported. Our case demonstrated a LVPG of 72. mmHg, and β-blockers were contraindicated because of bronchial asthma. Intravenous cibenzoline administration resulted in successful attenuation of the patient's LVPG. The present case suggests that cibenzoline might be effective for the treatment of takotsubo cardiomyopathy, especially in those contraindicated for β-blocker therapy.&gt
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DOI： 10.1016/j.jccase.2015.01.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 16-year-old boy stayed in Tokyo near Yoyogi Park for extracurricular high school activities. After returning home, he experienced an episode of fever and visited our emergency outpatient unit. He initially exhibited symptoms of leukopenia, thrombocytopenia and concomitant rhabdomyolysis and after admission simultaneously developed a biphasic fever and systemic erythema. Based on the results of reverse transcription polymerase chain reaction testing, he was finally diagnosed with dengue fever. After an absence of 70 years, dengue fever has reemerged as a domestic infection. Awareness of this trend led to our diagnosis.

DOI： 10.2169/internalmedicine.54.4094

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

An 84-year-old woman diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) was referred to our hospital due to chest pain associated with an increased level of troponin T. Following the administration of cibenzoline, the left ventricular outflow pressure gradient (LVPG) completely disappeared. Left ventricular pressure pullback tracing subsequently demonstrated the "reappearance" of the LVPG. Left ventriculography showed apical ballooning with excessive contractions at the base of heart, and we therefore made a diagnosis of Takotsubo cardiomyopathy in a patient with HOCM. Hypercontractions of the base of the heart associated with Takotsubo cardiomyopathy may be responsible for the "reappearance" of LVPG in this case.

DOI： 10.2169/internalmedicine.54.3868

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Language：English   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.4634

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

Background The CHADS2 scoring system is simple and widely accepted for predicting thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Although congestive heart failure (CHF) is a component of the CHADS2 score, the definition of CHF remains unclear. We previously reported that the presence of CHF was a strong predictor of left atrial appendage (LAA) thrombus. Therefore, the present study aimed to elucidate the relationship between LAA thrombus and the brain natriuretic peptide (BNP) level in patients with unanticoagulated NVAF. Methods The study included 524 consecutive patients with NVAF who had undergone transesophageal echocardiography to detect intracardiac thrombus before cardioversion between January 2006 and December 2008, at Hiroshima City Asa Hospital. The exclusion criteria were as follows: paroxysmal atrial fibrillation, unknown BNP levels, prothrombin time international normalized ratio ≥2.0, and hospitalization for systemic thromboembolism. Results Receiver operating characteristic analysis yielded optimal plasma BNP cut-off levels of 157.1 pg/mL (area under the curve, 0.91
p&lt
0.01) and 251.2 pg/mL (area under the curve, 0.70
p&lt
0.01) for identifying CHF and detecting LAA thrombus, respectively. Multivariate analyses demonstrated that a BNP level &gt
251.2 pg/mL was an independent predictor of LAA thrombus (odds ratio, 3.51
95% confidence interval, 1.08-10.7
p=0.046). Conclusions In patients with unanticoagulated NVAF, a BNP level &gt
251.2 pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF.

DOI： 10.1016/j.joa.2015.04.002

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We reviewed the natural history of patients with hypertrophic cardiomyopathy (HCM). The effect of medical treatments on natural history, left ventricular (LV) functions and LV remodeling was also evaluated. Sudden cardiac death and end-stage heart failure are the most serious complications of HCM. Age &lt;30 years and a family history of sudden premature death are risk factors for sudden cardiac death in HCM patients. End-stage heart failure is not a specific additional phenomenon observed in patients with HCM, but is the natural course of the disease in most of those patients. After the occurrence of heart failure, the progression to cardiac death is very rapid. Young age at diagnosis, a family history of HCM, and greater wall thickness are associated with a greater likelihood of developing end-stage heart failure. Neither beta-blockers nor calcium antagonists can prevent this transition.
The class la antiarrhythmic drugs, disopyramide and cibenzoline are useful for the reduction of LV pressure gradient. Unlike disopyramide, cibenzoline has little anticholinergic activity; therefore, this drug can be easily adapted to long-term use. In addition to the reduction in LV pressure gradient, cibenzoline can improve LV diastolic dysfunction, and induce regression of LV hypertrophy in patients with HCM. A decrease in intracellular Ca2+ concentration through the activation of the Na+/Ca2+ exchanger associated with cibenzoline therapy is likely to be closely related with the improvement in HCM-related disorders. It is possible that cibenzoline can prevent the progression from typical HCM to end-stage heart failure. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2014.02.022

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1161/CIRCULATIONAHA.113.002062

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In recent years, while therapeutic outcome after percutaneous coronary intervention is improving due to the introduction of drug-eluting stent and device development, procedure-related complications including coronary perforation may ineluctably occur though at low-frequency, even if careful manipulations are performed under IVUS guidance. Meanwhile, coronary pseudoaneurysm subsequent to coronary perforation is one of the complications at chronic phase infrequently experienced following percutaneous coronary intervention. To date, the incidence and natural history of pseudoaneurysm following coronary artery perforation remain unclear. We experienced a case with coronary pseudoaneurysm developed 2 weeks after Ellis II-type coronary artery perforation which spontaneously disappeared 4 months later. As the mechanism of disappearance, thrombotic occlusion was confirmed upon intravascular ultrasound. © 2013 Japanese Association of Cardiovascular Intervention and Therapeutics.

DOI： 10.1007/s12928-013-0181-0

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Background: An impaired myocardial perfusion state after primary angioplasty is a strong predictor of long-term adverse outcomes in patients with STEMI. We assessed the relationship between culprit plaque characteristics and myocardial perfusion state after primary angioplasty in patients with ST-segment elevation myocardial infarction (STEMI).
Methods: A total of 101 consecutive patients with de novo STEMI were divided into 3 groups according to the state of myocardial perfusion assessed by ST-segment elevation resolution (STR): Group A (complete: STR &gt;= 70%, n=26), Group B (partial: STR&lt;70% but &gt;= 30%, n=55) and Group C (none: STR&lt;30%, n=20). We analyzed plaque features by virtual histology intravascular ultrasound (VH-IVUS) and assessed the relationship between culprit plaque characteristics and STR after primary angioplasty.
Results: Total plaque volume was significantly higher in Group C than in Groups A and B (146.4 +/- 38.0 mm(3) vs. 93.3 +/- 29.1 mm(3) and 105.8 +/- 31.5 mm(3), p&lt;0.001, respectively). Necrotic core (NC) volume was also significantly higher in Group C than in Groups A and B (25.4 +/- 8.0 mm(3), vs. 11.9 +/- 6.3 mm(3) and 17.3 +/- 9.7 mm(3), p&lt;0.001, respectively). Analysis of receiver-operating characteristic curves revealed that total plaque volume and NC volume had the best diagnostic accuracy of all the VH-IVUS parameters to predict STR&lt;30%. The optimal cutoff values (sensitivity/specificity) were 123.4 mm(3) (75.0%/75.3%) for total plaque volume and 20.3 mm(3) (75.0%/74.1%) for NC volume.
Conclusions: Culprit plaque with large plaque burden and high NC volume is closely associated with poor STR after revascularization. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2012.03.079

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Establishing a symptom-rhythm correlation in patients with unexplained syncope is complicated because of its sporadic, infrequent, and unpredictable nature.Recently, an implantable loop recorder (ILR) has become available to evaluate undiagnosed recurrent arrhythmic episodes particularly in unexplained syncopes, and its usefulness has been reported in patients with recurrent syncopes that remain unexplained after conventional work-up.A 65-year-old man was referred to our hospital for loss of consciousness with nocturnal paroxysmal seizures. He had experienced several similar episodes. No family history of sudden death was evident, and apparent structural heart disease was absent. Coronary angiography with intracoronary ergonovine provocation showed vasospasm in left coronary artery without organic stenosis. Ventricular tachyarrhythmias were not induced by programmed electrical stimuli. According to the guideline, he was at once categorized as having class IIb indication for implantable cardioverter defibrillator implantation. However, his symptoms were not relieved despite administration of anti-anginal medications including nitrates and calcium antagonist. Implantation of an ILR was performed and revealed an episode of ventricular fibrillation during generalized-convulsion attack during sleep. ILR is useful in determining the presence of fatal arrhythmias during syncope, although conventional diagnostic testing, such as electrocardiogram, Holter monitoring, and external loop recording, is inconclusive. © 2012 Japanese College of Cardiology.

DOI： 10.1016/j.jccase.2012.06.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ Publishing Group  

A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands - with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death. Copyright 2012 BMJ Publishing Group. All rights reserved.

DOI： 10.1136/bcr-2012-006682

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Background: Plaque rupture plays a critical role for the development of acute myocardial infarction. However, whether quantitative parameters with regard to the cavity size of ruptured plaque are associated with no-reflow (NR) phenomenon following primary angioplasty remains to be elucidated.
Methods and results: A total of 53 patients with de novo ST-elevation myocardial infarction (STEMI) who had plaque rupture at the culprit lesion defined by pre-intervention virtual histology intravascular ultrasound (VH-IVUS) were enrolled. Patients were divided into two groups according to the presence of NR phenomenon: NR group (n = 19) and non-NR group (n=34). By VH-IVUS, we evaluated cavity length, maximum area, and volume of ruptured plaque in culprit lesions. The cavity length, maximum area, and volume were significantly higher in the NR group than those of the non-NR group (4.8 +/- 2.1 mm vs. 2.9 +/- 4.8 mm, p &lt; 0.001; 3.6 +/- 1.4 mm(2) vs. 1.9 +/- 0.5 mm(2), p &lt; 0.001; 11.5 +/- 6.3 mm(3) vs. 3.7 +/- 2.2 cm(3), p &lt; 0.001). A multiple logistic regression analysis revealed that the cavity volume was an independent risk for NR phenomenon. Receiver-operating characteristic analysis revealed that the cavity volume could predict NR phenomenon.
Conclusions: The cavity size of ruptured plaque is closely associated with NR phenomenon in patients with STEMI. Evaluation of the cavity volume by VH-IVUS may provide useful information for the prediction of NR phenomenon. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2010.08.002

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Background: The angiographic no-reflow phenomenon after primary percutaneous coronary intervention (PCI) carries a poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). However, the type of plaque composition that associates with the angiographic no-reflow phenomenon remains unclear.
Methods: A total of 44 patients with STEMI were enrolled in this study. After thrombectomy with an aspiration catheter, virtual histology intravascular ultrasound (VH-IVUS) of the infarct-related vessel was performed. Patients were divided into two groups according to final thrombolysis in myocardial infarction (TIMI) flow grade at the completion of PCI procedure. Complete reperfusion group (CR-group) was defined as final TIMI flow grade 3, and no-reflow group (NR-group) was defined as final TIMI flow &lt;= 2. The relationship between plaque composition and angiographic no-reflow phenomenon was analyzed.
Results: The angiographic no-reflow phenomenon was observed in 20 individuals. The summation of the percentage of fibrofatty + necrotic core and fibrofatty + dense calcium was significantly higher in the NR-group. Receiver-ope rating characteristics analysis revealed that the summation of the volume and percentage of fibrofatty + necrotic core (&gt;20.1 mm(3), 26.2%) and fibrofatty + dense calcium (&gt;20.0 mm(3), 22.6%) predict the angiographic no-flow phenomenon.
Conclusion: The fibrofatty-rich component with necrotic core or dense calcium derived from VH-IVUS is closely related to the angiographic no-reflow phenomenon observed in primary PCI. (C) 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2009.05.009

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 78-year-old man who suffered from syncope and lightheadedness during straining. The patient visited to our department for evaluation of his symptom. Cardiac auscultation revealed a grade II/IV systolic murmur along the left parasternal border. Electrocardiography showed T wave inversion at the right precordial leads. Echocardiography demonstrated an unruptured aneurysm originating at the sinus of Valsalva protruding into the right ventricular outflow tract. Cardiac cathtere- rization demonstrated a pressure gradient of 34 mmHg between the right ventricular cavity and pulmonary artery with a large aneurysm originating from the right coronary cusp. Because of his low activity of daily living owing to old cerebral infarction, we managed the patient conservatively.

DOI： 10.3143/geriatrics.46.259

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Background Cibenzoline is able to improve left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM), but the exact mechanism remains to be determined.
Methods and Results The present study was designed to elucidate the effect of intravenous administration of 1.4mg/kg of cibenzoline on aortic and LV pressures, and transmitral Doppler flow pattern in 7 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 9 patients with hypertrophic nonobstructive cardiomyopathy (HNCM). Before and at the end of the administration, aortic and LV pressures, LV pressure gradient (LVPG) and transmitral Doppler velocity profiles were examined. After the administration of cibenzoline, LV minimal and end-diastolic pressures decreased from 9 +/- 4 mmHg to 1 +/- 5 mmHg (p=0.0049) and from 22 +/- 7 mmHg to 14 +/- 5 mmHg (p=0.0106) in patients with HOCM, and from 9 +/- 5 mmHg to 5 +/- 3 mmHg (p=0.0036) and from 20 +/- 6mmHg to 14 +/- 3 mmHg (p=0.0033) in patients with HNCM. LVPG decreased in all patients with HOCM. E-wave velocity increased, A-wave velocity decreased, and thus the E/A ratio increased from 0.77 +/- 0.29 to 1.20 +/- 0.48 (p=0.0004).
Conclusions Reduction of LV diastolic pressures by intravenous administration of cibenzoline may be related to an improvement in the E/A ratio in patients with HCM.

DOI： 10.1253/circj.71.1540

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Background It was recently suggested that insulin resistance is significantly correlated with activation of the cardiac sympathetic nervous system in patients with essential hypertension.
Objectives To examine the effects of troglitazone, an agent used to treat insulin resistance, on cardiac sympathetic nervous dysfunction and insulin resistance in patients with essential hypertension.
Methods The study participants included 34 patients (14 men, 20 women) with mild essential hypertension and 17 normal controls (group C, seven men). The patients were randomly divided into two groups, one treated with 400 mg troglitazone and anti hypertensive drugs (group T, n = 17) and the other treated with anti hypertensive drugs only (group N, n = 17). We evaluated insulin resistance and cardiac sympathetic nervous function before and after 6 months of treatment. Insulin resistance was evaluated using steady-state plasma glucose (SSPG; mg/dl) concentrations and cardiac sympathetic nervous function was evaluated using the heart-to-mediastinum ratio (H: M) and mean washout rate measured by I-123-meta-iodobenzylguanidine (MIBG) cardiac imaging.
Results There were significant differences in SSPG (P &lt; 0.01), early (P &lt; 0.05) and delayed (P &lt; 0.05) phases of H : M and washout rate (P &lt; 0.05) between the hypertensive patients and group C. The SSPG concentration was significantly improved after treatment only in group T, from 153.3 to 123.7 mg/dl (P &lt; 0.01). The early and delayed phases of H : M and washout rate also were significantly improved (P &lt; 0.05) (from 2.59 to 2.63, from 2.12 to 2.27 and from 18.1 to 13.7%, respectively) in only group T.The change in SSPG was significantly correlated with the changes in H : M and washout rate (r = -0.639 and 0.577, respectively).
Conclusion Troglitazone had a beneficial effect on cardiac sympathetic nervous function through a decrease in insulin resistance in patients with essential hypertension. (C) 2004 Lippincott Williams Wilkins.

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We examined the effects of cilostozol on impaired coronary arterial responses in patients with vasospastic angina (VSA). Thirty patients who were diagnosed with VSA based on an acetylcholine provocation test and 10 subjects with normal coronary arteries were enrolled. The patients were divided into the following 3 groups: no antiplatelet agent treatment group, aspirin treatment, or cilostozol treatment groups. Coronary flow reserve (CFR), coronary flow volume at maximum hyperemia, and epicardial coronary artery diameter after administration of N-G-monomethyl-L-arginine (L-NMMA) were examined using a Doppler flow wire before and 6 months after the start of this study. CFR, coronary flow volume at maximum hyperemia, and diameter changes by L-NMMA were significantly increased in the cilostazol treatment group compared with the other 2 groups. in conclusion, cilostazol increased CFR and flow-dependent coronary dilation; these changes were attributable to nitric oxide. Cilostazol may improve coronary vascular endothelial dysfunction and coronary hemodynamics in patients with VSA. (C)2003 by Excerpta Medica, Inc.

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Background : Cardiologists who implant cardiovascular implantable electronic devices (CIED) should receive operative training and have a detailed knowledge of human anatomy. In other countries, cadaver training has become very common, but, it is not common in Japan. We report the first experience of cadaver training for the implantation of CIED in Japan. Methods : Cadaver training was performed in accordance with the guideline &ldquo;Autopsy for clinical medicine training and research&rdquo; and was approved by the institutional research board of Ehime University School of Medicine. Cadavers were embalmed with Thiel solution. We implanted CIED leads (active fixation leads) in cadavers under fluoroscopic guidance. After implantation, we autopsied the cadavers for anatomical evaluation. Results : CIED implantation by the subclavian vein approach could be performed on cadavers. However, cadaver training revealed that atrial lead implantation was difficult because cadavers did not have any spontaneous circulation. After autopsy, important anatomical structures such as the costoclavicular ligaments, phrenic nerves, and arteriovenous vessels could be observed in detail. Common sites for lead perforation included the right atrial appendage, right atrial and ventricular free wall, and right ventricular apex. We compared fluoroscopic images with the true anatomy with respect to lead location, and there were discrepancies between them. Conclusion : Cadaver training is useful for cardiologists who implant CIED to learn about anatomy and operative procedures.

DOI： 10.5105/jse.37.12

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Background : Cardiologists who implant cardiovascular implantable electronic devices (CIED) should receive operative training and have a detailed knowledge of human anatomy. In other countries, cadaver training has become very common, but, it is not common in Japan. We report the first experience of cadaver training for the implantation of CIED in Japan. Methods : Cadaver training was performed in accordance with the guideline &ldquo;Autopsy for clinical medicine training and research&rdquo; and was approved by the institutional research board of Ehime University School of Medicine. Cadavers were embalmed with Thiel solution. We implanted CIED leads (active fixation leads) in cadavers under fluoroscopic guidance. After implantation, we autopsied the cadavers for anatomical evaluation. Results : CIED implantation by the subclavian vein approach could be performed on cadavers. However, cadaver training revealed that atrial lead implantation was difficult because cadavers did not have any spontaneous circulation. After autopsy, important anatomical structures such as the costoclavicular ligaments, phrenic nerves, and arteriovenous vessels could be observed in detail. Common sites for lead perforation included the right atrial appendage, right atrial and ventricular free wall, and right ventricular apex. We compared fluoroscopic images with the true anatomy with respect to lead location, and there were discrepancies between them. Conclusion : Cadaver training is useful for cardiologists who implant CIED to learn about anatomy and operative procedures.

DOI： 10.5105/jse.37.12

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DOI： 10.2143/AC.71.6.3178195

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DOI： 10.11281/shinzo.46.1476

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症例は75歳, 女性. 2日前からの胸痛を主訴に近医を受診, 急性冠症候群を疑われ当院に紹介された. 心電図にてV&lt;sub&gt;3&lt;/sub&gt;～V&lt;sub&gt;5&lt;/sub&gt;の陰性T波, 心エコー図で前壁の壁運動低下および155mmHgの左室内圧較差を認めた. 緊急で冠動脈造影を施行したが有意狭窄は認めず, 左室造影上はいわゆる &quot;たこつぼ&quot; 型を呈していた. エルゴノビン負荷による冠攣縮誘発試験は陰性であり, 左室心尖部から心基部への引抜き圧較差は約130mmHgであった. 帰室中に心停止となった. 心破裂と診断し蘇生下心嚢ドレナージにて血圧上昇と意識回復を認めた. 緊急開胸術を施行し第30病日軽快退院した. たこつぼ心筋症から心破裂にいたり救命し得た症例は非常に稀であり報告する.

DOI： 10.11281/shinzo.46.1476

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A 78-year-old man who suffered from syncope and lightheadedness during straining. The patient visited to our department for evaluation of his symptom. Cardiac auscultation revealed a grade II/IV systolic murmur along the left parasternal border. Electrocardiography showed T wave inversion at the right precordial leads. Echocardiography demonstrated an unruptured aneurysm originating at the sinus of Valsalva protruding into the right ventricular outflow tract. Cardiac cathtere- rization demonstrated a pressure gradient of 34 mmHg between the right ventricular cavity and pulmonary artery with a large aneurysm originating from the right coronary cusp. Because of his low activity of daily living owing to old cerebral infarction, we managed the patient conservatively.

DOI： 10.3143/geriatrics.46.259

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An 83-year-old male was diagnosed with acute inferior myocardial infarction and underwent emergency percutaneous coronary intervention (PCI). During primary PCI for the right coronary artery, we experienced coronary perforation induced by the hydrophilic guidewire. We successfully controled the bleeding from the perforated site by embolization with the patient&#039;s own subcutaneous fat tissue taken from the puncture site. Coronary perforation induced by hydrophilic guidewire occurs not only while trying to cross the culprit lesion but also all throughout the wire manipulation process. For prevention and early detection of wire-induced perforation, it is important to watch for the tip of the guidewire during all procedural processes. In case of coronary perforation, prompt management based on angiographic classification and therapeutic algorithm is required to prevent of cardiac tamponade. Embolization by fat tissue is a more rapid and simple method than other embolic procedures.

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DOI： 10.1253/circj.71.880

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