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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC.CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

A 17-year-old boy with acute coronary syndrome was admitted to our hospital. He had xanthomas over his elbow and Achilles tendon and a high level of low-density lipoprotein cholesterol; therefore, his initial diagnosis was familial hypercholesterolemia. However, a genetic analysis revealed a compound heterozygous mutation in the ABCG5 gene with a high serum level of sitosterol, leading to the diagnosis of sitosterolemia. After lipid-lowering treatment, percutaneous coronary intervention was performed. Furthermore, a persistently high C-reactive protein level and images of large arteries led to a diagnosis of Takayasu arteritis. To our knowledge, this is the first case of sitosterolemia complicated by Takayasu arteritis.

Background The cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness and has been reported to be associated with the severity of coronary artery disease and cardiovascular events. However, whether CAVI can predict the composition of coronary plaques remains unclear. Methods We enrolled 208 patients who underwent percutaneous coronary intervention (PCI) for culprit lesions evaluated with iMAP-intravascular ultrasound (IVUS), a radiofrequency imaging system for characterizing tissues. iMAP-IVUS classified the culprit plaque composition as fibrotic, lipidic, necrotic, or calcified, and the respective absolute volumes [fibrotic volume (FV), lipidic volume (LV), necrotic volume NV, and calcified volume] and their ratios (%) within the total plaque volume were calculated. A plaque with a median %NV of ≥ 33.2% was defined as a larger NV (LNV) plaque. We measured CAVI and divided the patients into two groups according to CAVI ≥8 (high CAVI, n = 164) or Results Culprit plaques had significantly greater absolute NV (p = 0.016), %NV (p = 0.01), and smaller %FV (p = 0.02) in patients with high CAVI than in those with low CAVI. Patients with high CAVI had a higher prevalence of LNV plaques in culprit lesions than those with low CAVI (54% vs. 34%, p = 0.026). CAVI correlated significantly and positively with absolute NV, LV, and negatively with %FV. In logistic regression analysis after adjustment for the classic coronary risk factors and possible variables associated with vulnerable plaques, high CAVI had an independent and significant association with the presence of LNV plaques (OR, 3.37; 95% CI, 1.45–7.79; p = 0.0032). Conclusions A high CAVI is associated with the composition of coronary culprit plaques, particularly increased amount of necrotic tissue, in patients with coronary artery disease undergoing PCI .

Background: Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent upper gastrointestinal bleeding in patients undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of both vonoprazan and prasugrel. This raises concern about the possibility of a CYP3A4-mediated drug-drug interaction between vonoprazan and prasugrel that may lead to attenuation of prasugrel's antiplatelet effect. Methods and Results: We evaluated 88 PCI patients who were taking either vonoprazan (n=45) or proton pump inhibitors (PPIs; n=43) in combination with DAPT (aspirin and prasugrel). Platelet reactivity on prasugrel was assessed using the VerifyNow P2Y12 assay. The primary endpoint was comparison of P2Y12 reaction units (PRU) between patients on vonoprazan and PPIs. PRU >208 and

Objective Associations between aortic stiffness and cardiovascular disease events are mediated in part by pathways that include coronary microvascular dysfunction (CMD) and remodeling. However, the relationship between aortic stiffness and CMD remains unclear. The present study aimed to determine whether aortic stiffness causes CMD as evaluated by the hyperemic microvascular resistance index (hMVRI) in patients with non-obstructive coronary artery disease (CAD). Methods The intracoronary physiological variables in 209 coronary arteries were evaluated in 121 patients with non-obstructive CAD (fractional flow reserve >0.80) or reference vessels. The cardio-ankle vascular index (CAVI) as a measure of aortic stiffness and atherosclerotic risk factors were also measured. Results Univariate analyses showed that hMVRI correlated with age (β=0.24, p=0.007), eicosapentaenoic acid (EPA; β=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (β=-0.22, p=0.014) and CAVI (β=0.30, p=0.001). A multivariate regression analysis identified CAVI (β=0.25, p=0.007) and EPA/AA ratio (β=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI. Conclusion Aortic stiffness may cause CMD in patients with non-obstructive CAD via increased coronary microvascular resistance. Aortic stiffness is associated with CMD which is evaluated as hyperemic microvascular resistance in patients with non-obstructive CAD.

Background: Dual antiplatelet therapy with aspirin and P2Y12 receptor inhibitor is an important option for preventing acute stent thrombosis after percutaneous coronary intervention (PCI). Case summary: A 72-year-old man was admitted to our hospital with ST-segment elevation myocardial infarction. Emergent coronary angiography identified the occlusion in the proximal left anterior descending artery. This lesion was successfully treated by thrombus aspiration and an everolimus-eluting platinum chromium stent implantation with loading of aspirin 200 mg and prasugrel 20 mg. However, acute closure of the stent occurred 1 h after PCI. P2Y12 reaction units (PRU) measured using VerifyNow assay was 282, suggesting high platelet reactivity on prasugrel. After adding cilostazol 200 mg, recanalization was successfully obtained by thrombus aspiration and ballooning under intra-aortic balloon pump. Thereafter, PRU decreased to 266 at 4 h after PCI, and 49 the next day, implying full inhibition of platelet reactivity on prasugrel. Fortunately, no stent thrombosis has recurred since then. Genotype analysis of cytochrome P450 enzyme (CYP) demonstrated CYP2B6?1/?2 polymorphism leading to impaired metabolism of prasugrel. Based on these findings, acute stent thrombosis in the present case might have been caused by delayed expression of prasugrel effects due to CYP2B6?2 (C64T) polymorphism. Discussion: In cases of stent thrombosis, we should consider the possibility of poor response to P2Y12 receptor inhibitors due to CYP polymorphism. Assessment of platelet aggregation and CYP genotype may be warranted., European Heart Journal - Case Reports, 4(4), pp.1-7; 2020

Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents.Methods and Results:This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis.The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.

A 73-year-old Japanese man was admitted with extreme intradialytic hypertension of four months’ duration that was refractory to antihypertensive agents. He had started hemodialysis five years previously because of diabetic nephropathy. Coronary angiography revealed coronary artery disease with significant stenosis of the left main trunk and the right coronary artery, and he underwent a coronary artery bypass graft. Thereafter, the intradialytic hypertension disappeared. Ischemic heart disease appears to be one cause of intradialytic hypertension.

A 65-year-old Japanese woman with an intrapericardial tumor and neck tumor was admitted to our hospital. Intrapericardial tumor had not been resected because of massive bleeding from the hypervascular tumor and its invasion into the pericardium, ascending aorta, and pulmonary artery. The neck tumor had been successfully resected, and paraganglioma was pathologically diagnosed. Abnormal accumulation in the intrapericardial tumor was seen with (123)I-metaiodobenzylguanidine scintigraphy. Moreover, gene mutation of succinate dehydrogenase type D was found. Finally, paraganglioma of the carotid body and intrapericardium was diagnosed.

A 45-year-old Japanese man was referred to our hospital with chest and back pain with a duration of two days. Contrast-enhanced computed tomography (CT) showed a large calcified lesion in the inferior vena cava (IVC),thrombus with calcification in the pulmonary arteries of the left lower lobe, and an infiltrative shadow in the left lower lobe. He was diagnosed with pulmonary thromboembolism (PE) and pneumonia. Calcification in the IVC was not evident on any CT images obtained six and eight years earlier. This patient was identified to be an extremely rare case of PE associated with IVC calcification that developed during adulthood., Internal medicine, 58(13), pp.1907-1912; 2019

This study examined whether using an artificial neural network (ANN) helps beginners in diagnostic cardiac imaging to achieve similar results to experts when interpreting stress myocardial perfusion imaging (MPI). One hundred and thirty-eight patients underwent stress MPI with Tc-labeled agents. An expert and a beginner interpreted stress/rest MPI with or without the ANN and the results were compared. The myocardium was divided into 5 regions (the apex; septum; anterior; lateral, and inferior regions), and the defect score of myocardial blood flow was evaluated from 0 to 4, and SSS, SRS, and SDS were calculated. The ANN effect, defined as the difference in each of these scores between with and without the ANN, was calculated to investigate the influence of ANN on the interpreters' performance. We classified 2 groups (insignificant perfusion group and significant perfusion group) and compared them. In the same way, classified 2 groups (insignificant ischemia group and significant ischemia group) and compared them. Besides, we classified 2 groups (normal vessels group and multi-vessels group) and compared them. The ANN effect was smaller for the expert than for the beginner. Besides, the ANN effect for insignificant perfusion group, insignificant ischemia group and multi-vessels group were smaller for the expert than for the beginner. On the other hand, the ANN effect for significant perfusion group, significant ischemia group and normal vessels group were no significant. When interpreting MPI, beginners may achieve similar results to experts by using an ANN. Thus, interpreting MPI with ANN may be useful for beginners. Furthermore, when beginners interpret insignificant perfusion group, insignificant ischemia group and multi-vessel group, beginners may achieve similar results to experts by using an ANN.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD.CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38,460 pg/mL).The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate60 mL/min/1.73 mHigh serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD). Intracoronary physiological variables (fractional flow reserve (FFR),hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (β = ?0.31, P = 0.001) and EPA (β = ?0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (β = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (β = ?0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (β = 0.26, P = 0.008) but not with Pd at hyperemia. A lower serum EPA/AA ratio may cause CMD in patients with stable CAD., International Heart Journal, 59(6), pp.1194-1201; 2018

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients’ demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients’ demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p

Electrocardiography (ECG) is used to screen for pulmonary hypertension (PH). However, it is unclear which parameters of ECG are the most useful for screening.ECG parameters related to right ventricular hypertrophy criteria were examined in 145 ECGs of subjects who were suspected to have PH and underwent right heart catheterization (RHC) (age 58.4 ± 17.5 years, 112 women, mean pulmonary arterial pressure [MPAP] 35.4 ± 13.3 mmHg). Based on the results of RHC, 108 subjects had PH (56 pulmonary arterial hypertension [PAH] and 52 chronic thromboembolic pulmonary hypertension [CTEPH]).Fourteen of 17 ECG parameters in the present study were significantly associated with PH on univariate analysis. On multivariable logistic regression analysis, S wave depth in lead V5 (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.10-1.47) and depth of T wave inversion in lead V4 (OR 1.21, 95% CI 1.03-1.46) were independent predictors of MPAP ≥ 25 mmHg, and the cut-off values determined by receiver operating characteristic curve analyses were 0.42 mV and -0.28 mV, respectively.In conclusion, a deeper S wave in lead V5 and the presence of a wider extent of negative T waves in the precordial leads may be clinically simple and useful ECG parameters for screening for PH.

AIM Balloon pulmonary angioplasty (BPA) has recently been established as an effective therapy for peripheral-type chronic thromboembolic pulmonary hypertension (CTEPH). However, the safety and effectiveness of BPA in elderly patients with CTEPH have not been clarified. METHODS A total of 19 patients with CTEPH who underwent BPA were recruited. The patients were assigned to groups by age

Calcified amorphous tumor (CAT) is a rare, non-neoplastic tumor involving calcium deposition in amorphous materials. Although its etiology is unknown, cases have frequently been reported in patients with hemodialysis for chronic kidney disease. We herein describe a case of cardiac CAT in a 64-year-old woman who had been on hemodialysis for diabetic nephropathy for 20 years, and the findings of the present patient, in association with the findings of previous case reports, suggest that end-stage renal disease seems to play an important role in the onset of CAT, especially in CAT formation at the mitral annulus, which appears to differ from CAT occurring at other sites., Internal Medicine, 56(22), pp.3057-3060; 2017

A 73-year-old man was admitted with sudden onset of dyspnea. Contrast-enhanced computed tomography showed acute pulmonary thromboembolism and deep vein thrombosis. He was started on the direct oral anticoagulant rivaroxaban (factor Xa inhibitor) and this resolved the thrombus. Serological analysis revealed that his risk of thrombosis was primary antiphospholipid syndrome (APS). He has remained free of recurrent venous thromboembolism (VTE) for two years while under rivaroxaban. We present a case with VTE due to APS for whom direct oral anticoagulant was effective.

Background Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined. Purpose The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease. Methods We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index 460 pg/mL). Results Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p Conclusions Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.

A 63-year-old Japanese woman with an adrenal tumor was transferred to our hospital due to cardiogenic shock. Right and left ventriculography showed severe hypokinesis of the middle segment and the apex in both ventricles, and an endomyocardial biopsy demonstrated a small number of necrotic myocytes and cellular infiltration. She was diagnosed with pheochromocytoma and quickly recovered after treatment with an α-blocker. The functional disability of both the right and left ventricles with less myocardial damage due to an excessive level of catecholamine seemed to be related to the early recovery the present patient with catecholamine-induced cardiomyopathy due to pheochromocytoma., Internal Medicine, 56(6), pp.665-671; 2017

A 72-year-old individual with hypertension and 5-year history of chronic myeloid leukemia under therapy with tyrosine kinase inhibitor nilotinib was referred to us with intermittent claudication due to chronic total occlusion of bilateral superficial femoral arteries (SFA). He had undergone

Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown. The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048). Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC., International Heart Journal, 56(6), pp.626-631; 2015

BACKGROUND The ability of iMap-intravascular ultrasound (IVUS) tissue characterization to detect thin-cap fibroatheroma (TCFA) identified on optical coherence tomography (OCT) has not yet been fully elucidated. METHODS AND RESULTS We evaluated 86 coronary lesions from 73 patients with stable angina pectoris using iMap-IVUS and OCT. We defined OCT-derived TCFA (OCT-TCFA) as lipid-rich plaque with a

The transradial approach has been used for coronary procedures, but this procedure carries a risk of injury to the endothelium of the radial artery. In this study, the vascular dysfunction caused by transradial catheterization was examined using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently developed technique for assessing endothelial function in digits, and the differences in injuries were compared according to the size of sheath.Forty-three patients undergoing transradial catheterization with 6-Fr sheaths (n = 17) or 4-Fr/5-Fr (non-6-Fr; n = 26) sheaths underwent RH-PAT using an Endo-PAT2000 before, the day after, and 6 months after catheterization. RH-PAT was assessed in the arm of sheath placement and in the other arm as a control.RH-PAT values decreased from 2.42 ± 0.67 before catheterization to 2.08 ± 0.41 the day after catheterization in the 6-Fr group (P = 0.031); this was more evident in patients with a longer procedure time (> 91 minutes). In contrast, the change in the non-6-Fr group was not significant. RH-PAT of the non-catheterized arm was unchanged in both groups. At 6 months after catheterization, RH-PAT values in the 6-Fr group had not completely returned to baseline.In conclusion, the insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function assessed by RH-PAT the day after the procedure and was sustained for 6 months. Thus, the use of smaller size sheaths (< 6-Fr) with a shorter procedure should be considered when performing transradial catheterization.

Objective Coronary artery disease (CAD) is one of the clinical categories of atherosclerotic diseases. There have been reports indicating that the pathological findings of coronary artery plaque differ between acute coronary syndrome (ACS) and effort angina pectoris (EAP). The brachial-ankle pulse wave velocity (baPWV) has been reported to be a good indicator of atherosclerotic disease. However, the baPWV may not be equally effective for evaluating ACS and EAP. In this study, we compared the baPWV in patients with ACS and those with EAP. Methods Two hundred and seventy patients were enrolled in this study. All patients underwent coronary angiography, and were separated into normal (CONT), ACS and EAP groups according to the clinical and coronary angiographic findings. The baPWV was evaluated and the results were compared among the groups. Results The baPWV was significantly higher in the EAP group than in the other groups. The baPWV in the ACS group was almost the same as that of the CONT group and was significantly higher in the EAP group than in the ACS group across almost all age groups. Conclusion The present study showed that the baPWV is high in patients with EAP. In contrast, the baPWV in the ACS group was almost normal and was similar to that of the CONT group. ACS occurs due to plaque rupture induced by atherosis, which may occur independent of sclerosis in the coronary artery. EAP may occur in proportion to systemic arterial sclerosis. The baPWV is suitable for screening for EAP, but not for ACS., Internal Medicine, 57(10), pp.1371-1374; 2018

Balloon pulmonary angioplasty (BPA) has recently been established as an effective therapy for peripheral-type chronic thromboembolic pulmonary hypertension (CTEPH). However, the safety and effectiveness of BPA in elderly patients with CTEPH have not been clarified.A total of 19 patients with CTEPH who underwent BPA were recruited. The patients were assigned to groups by age,70 years (non-elderly; n = 11) and ≥70 years (elderly; n = 8). Hemodynamic parameters, right ventricular function and plasma N-terminal pro-brain natriuretic peptide were assessed before and after BPA, and complications arising after BPA were also evaluated.Hemodynamic parameters and right heart function did not differ significantly between the two groups at baseline. BPA significantly improved pulmonary arterial pressure, pulmonary vascular resistance and fractional area change in both groups (all P0.05), although the differences were comparable. No fatal complications developed, but the frequency of minor complications, such as transient hemoptysis, was higher in the elderly group than in the non-elderly group (median 0.45 [interquartile range 0.27-0.63] vs 0 [0-0.33], respectively; P = 0.021). The frequency of such complications was also higher in patients with a psychiatric disorder than in those without (0.50 [0.44-1.00] vs 0.14 [0-0.33], respectively; P = 0.006). Multivariate regression analysis identified higher age, baseline N-terminal pro-brain natriuretic peptide values and an underlying psychiatric disorder as significant predictors of complications of BPA.BPA is an effective treatment for peripheral-type CTEPH regardless of age; however, higher age, N-terminal pro-brain natriuretic peptide values before treatment and an underlying psychiatric disorder might be associated with minor complications. Geriatr Gerontol Int 2018; 18: 678-684.

Background: The long-term prognosis of coronary artery disease (CAD) patients with insulin resistance has not been fully examined. In this study, we investigated the influence of postload hyperinsulinemia (PHI) after a 75-g oral glucose tolerance test (OGTT), on the long-term prognosis of CAD patients. Methods: All study patients were diagnosed as having CAD by coronary angiography. The OGTT was performed for all patients to establish their blood glucose. Measurement of serum insulin was also performed simultaneously. Patients with 2-h insulin level of ?. 64. mU/l after the OGTT were included in the postload hyperinsulinemia (PHI) group, and the others were included in the non-PHI group. The prognosis of 208 patients (96 from the PHI group and 112 from the non-PHI group) was retrospectively investigated. Study end points were the composite of death from any cause, unexpected hospitalization for heart failure, new-onset ACS, angina pectoris requiring PCI or CABG, cerebrovascular disease (CVD), and peripheral artery disease (PAD). Variables were compared using Kaplan-Meier analysis and the log-rank tests. Results: The mean follow-up period was 78.7. months. Cardiovascular events including death were 40.6% in the PHI group and 23.2% in the non-PHI group (log-rank p = 0.0144). CVD, PCI, and CABG occurred continuously from early to late stage of follow-up in the PHI group compared with the non-PHI group. Conclusions: The present study showed that the prognosis of CHD patients with PHI was poor. Thus, it is important to pay attention to these conditions for improving the prognosis of CAD patients., IJC Metabolic & Endocrine, 5, pp.7-10; 2014

A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy., International Heart Journal, 56(6), pp.661-663; 2015

The left internal thoracic artery (LITA) is considered the most reliable coronary artery bypass grafting conduit due to its high rate of long-term patency. LITA grafts are extremely durable and associated complications are infrequent. We present a case with spontaneous spiral dissection of a LITA graft to the left anterior descending artery, which was assessed by optical coherence tomography (OCT) and intravascular ultrasound (IVUS). OCT was superior in visualizing the disrupted flap, false lumen, and intramural hematoma, but it did not visualize the full extent of the vessel wall. In contrast, IVUS allowed more complete and deeper vessel visualization, and thus better appreciation of the extent of intramural hematoma. Combined use of these two modalities provides complementary details on imaging of a LITA dissection., International Heart Journal, 56(3), pp.360-362; 2015

An infl ammatory response is a key event for endothelial dysfunction. Pentraxin 3 (PTX3) is an infl ammatory protein produced at infl ammation sites such as leukocytes and vascular endothelial cells. Here, we compared the relationships between endothelial function assessed by flow-mediated dilation (FMD), and the levels of plasma PTX3 and highsensitive C-reactive protein (hsCRP), another infl ammatory protein of the pentraxin family. Levels of FMD, PTX3 and hsCRP were measured twice within 6 to 8 months and retrospectively analyzed in 36 patients with coronary artery disease. We examined the associations between the values of FMD and the levels of PTX3 and hsCRP at the fi rst measurement, and between the change ratios (second value/fi rst value) of these parameters. Univariate linear regression analysis showed significantly negative correlations between FMD values and PTX3 and hsCRP levels at the fi rst measurement, and significant associations with taking statins or calcium antagonists. Multivariate linear stepwise regression analysis identifi ed PTX3 levels and taking statins and calcium antagonists as independent factors for endothelial function. The change ratio of FMD correlated more closely with that of PTX3 than of hsCRP (r =-0.446, P = 0.006 versus r =-0.330, P = 0.050). Significantly more patients with decreased FMD values had increased levels of PTX3 than those of hsCRP at the second measurement compared with the fi rst measurement. Furthermore, the ratio of patients with increased PTX3, but not increased hsCRP, was significantly reduced among those with increased, rather than decreased, FMD values. Endothelial dysfunction might be more accurately predicted by plasma PTX3 levels than by serum hsCRP levels., International Heart Journal, 55(2), pp.160-164; 2014

The report describes a case of penetration of an inferior vena cava filter (IVCF) strut through an introducer sheath inserted from the left internal jugular vein. A 64-year-old woman was admitted to our hospital with pulmonary embolism and lower extremity deep vein thrombosis. We attempted to implant a retrievable type IVCF via the left internal jugular vein. However, an unexpected resistance occurred during the advancement of the filter after passing the first few inches within the 8-Fr introducer sheath. Immediately, we checked the insertion site using fluoroscopy, which demonstrated penetration of the filter struts to the outside of the sheath. We speculate that a strong angulation in the vessel from the left internal jugular to superior vena cava might have contributed to this rare complication. Learning objective: Penetration of an inferior vena cava filter (IVCF) strut through an introducer sheath is a rare complication. However, physicians should recognize that this complication could occur in cases of IVCF placement, especially when insertion is done via the left internal jugular vein.>

Treatment options for chronic renal artery dissection, which is a rare cause of renal artery stenosis and renovascular hypertension, such as medical management, percutaneous intervention, and open surgical repair remain controversial. We describe a 55-year-old man with a chronic dissecting aneurysm of a renal artery complicated with renovascular hypertension that was initially diagnosed by computed tomography angiography, evaluated by intravascular ultrasound, and treated by stent implantation with coil embolization.© 2012 Wiley Periodicals, Inc.

The high resolution of optical coherence tomography (OCT) provides detailed information about coronary plaque morphology, which enables the mechanism of acute myocardial infarction to be evaluated. We describe two patients with acute myocardial infarction in whom culprit segments were identified by OCT, but not by either coronary angiography or intravascular ultrasound., Cardiovascular Intervention and Therapeutics, 27(1), pp.47-51; 2012

Objective Abnormal left ventricular (LV) geometry, especially concentric hypertrophy, is associated with cardiovascular morbidity and mortality. The aim of this study was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) and the effects of nasal continuous positive airway pressure (CPAP) on the LV geometric patterns. Methods The LV morphological parameters, including the LV mass index (LVMI) and the relative wall thickness (RWT), were evaluated using echocardiography in 37 patients with OSAS diagnosed on polysomnography and 34 control subjects. Based on the values of LVMI and RWT, the LV geometry was classified as normal, concentric remodeling, concentric hypertrophy or eccentric hypertrophy. The echocardiographic parameters were reassessed after three months of CPAP treatment. Results Compared with the controls, the OSAS patients had a higher proportion of concentric hypertrophy patterns (54% vs. 0%, p, Internal Medicine, 51(20), pp.2863-2868; 2012