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Background and Aims: Measurement of coronary microvascular resistance (MR) is essential for diagnosing nonocclusive coronary artery ischemia, but whether coronary branches of different diameters can be similarly assessed using hyperemic microvascular resistance index (hMVRI) calculated from average peak velocity (APV) remains unclear. We investigated the relationship between coronary arteries of different diameters and hMVRI. Methods: Thirty patients with suspected angina pectoris and nonobstructive coronary stenosis with fractional flow reserve >0.8 underwent evaluation of all coronary arteries using a Doppler velocity and pressure‐equipped guidewire. Quantitative coronary angiography (QCA) was used to analyze vessel diameter (DQCA). Coronary blood flow (CBFQCA) was calculated as πDQCA2/4 (0.5 × APV) and hMVRIQCA as distal coronary pressure divided by CBFQCA during maximal hyperemia. Results: The hMVRI was significantly higher for the right coronary artery than for the left anterior descending artery, but no significant differences between arteries were seen for CBFQCA and hMVRIQCA. Although the correlation between CBFQCA and APV was weak, CBFQCA divided into three groups according to DQCA showed very strong correlations with APV. Slopes of the straight line between APV and CBFQCA for small‐, middle‐, and large‐diameter groups were 0.48, 0.30, and 0.21, respectively, with slope decreasing as diameter increased. Conclusions: Comparative evaluation of MR in coronary branches with varying vessel diameters requires vessel diameter to be accounted for. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non‐T2DM]; women, n = 107 [T2DM] and n = 313 [non‐T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5‐year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age‐adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE) is a progressive hereditary disease that affects tissues such as the skin, retina, blood vessels, and gastrointestinal tracts. Therefore, comprehensive medical care across clinical departments specialized in specific organs is needed to provide the best clinical practices to PXE patients. The Japanese version of clinical guidelines developed by the Japanese Dermatological Association was published in 2017, and aimed to promote equal accessibility of PXE‐related medical care. Here, the English version of Japanese guideline is reported, and is intended to be worldwide reference for medical care of PXE. [ABSTRACT FROM AUTHOR]

Chronic myocarditis is sometimes difficult to diagnose using several clinical diagnostic modalities. A 43‐year‐old Japanese man was admitted to our hospital with heart failure due to a diffusely hypokinetic left ventricle. No abnormal accumulation was seen on 18F‐fluorodeoxyglucose positron emission tomography/computed tomography. Coronary angiography showed no abnormalities. Endomyocardial biopsy was performed on suspicion of dilated cardiomyopathy, revealing diffuse cell infiltration (more T lymphocytes associated with macrophages than B cells on immunohistochemical staining), myocyte damage, and replacement fibrosis. The pathological diagnosis of biopsy specimen was difficult to differentiate between chronic myocarditis and inflammatory dilated cardiomyopathy without immunohistochemistry. Endomyocardial biopsy offers one of the most useful methods for diagnosing chronic myocarditis. [ABSTRACT FROM AUTHOR]

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, <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. Results: 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 P < 0.05), 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. Conclusions: 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 [ABSTRACT FROM AUTHOR]

The article presents a case study of a 85 year old woman who underwent a nephrostomy for right hydronephrosis. It notes that after the surgery she suffered acute heart failure and several tests revealed that she was diagnosed with midventricular Takotsubo (or stress-induced) cardiomyopathy (TC). The article discusses that the patient's condition improved due to the infusion of landiolol and was released from the hospital after two days.

Pseudoxanthoma elasticum ( PXE) is a hereditary disease, causing calcification and degeneration of elastic fibers, which affects the skin, eye, cardiovascular systems and gastrointestinal tract. PXE is caused by mutations in the ABCC6 gene. Neither detailed nor large-scale analyses have been accomplished in Japanese patients with PXE. We, therefore, investigated clinical symptoms and ABCC6 gene mutations in 76 Japanese patients. Japanese PXE patients ( n = 76) had a significantly lower incidence of vascular lesions than 505 PXE patients in the Leiden Open Variation Database ( LOVD) (38.7% vs 65.1%, respectively; P = 1.34E-06); however, the incidences of the skin, eye, cardiac and gastrointestinal lesion symptoms were not significantly different. Symptom severity scores for skin, eye and vascular lesions, calculated using the Phenodex™ system, were significantly lower in Japanese PXE patients than in LOVD PXE patients. Genetic analysis revealed three nonsense, four frame-shift, one exon deletion and 13 missense mutations in ABCC6 in 73 patients; however, we were unable to detect pathogenic mutations in three patients. Frequent mutations differed between Japanese and LOVD PXE patients. In Japanese PXE patients, the top five mutations accounted for more than 60% of all pathogenic changes, suggesting the presence of founder effects. Consistent with previous reports, no obvious correlations between genotypes and phenotypes were identified in this study. In conclusion, we consider that the milder clinical phenotypes, observed even in older Japanese PXE patients, could be attributed to environmental factors such as dietary habits and lifestyle, as well as genetic background. [ABSTRACT FROM AUTHOR]

Leg malperfusion caused by dynamic obstruction is a serious complication of aortic dissection. A diagnosis of the malperfusion is difficult because it is made mainly on the basis of nonspecific symptoms such as intermittent claudication and numbness on walking. In the present study, we reported on a case of a 51‐year‐old man with leg malperfusion in chronic aortic dissection diagnosed by Doppler ultrasound. The combination of bisferious and dampened velocity waveform changes after walking may lead us to suspect a leg malperfusion caused by dynamic obstruction. [ABSTRACT FROM AUTHOR]

Background: Although ventricular premature contraction (VPC) commonly arises in subjects with and without heart diseases, the prognosis of VPC has remained controversial and the effect of their morphology on mortality has not been fully determined in subjects without obvious heart diseases. The objective of this study was to assess the morphologic effect of VPC on mortality.Methods: Japanese atomic bomb survivors (n = 6685) underwent baseline health examinations and standard 12-lead electrocardiogram (ECG) between January 1990 and December 1991. Of these, we extracted data from 5,685 (67.1% women) subjects who had neither heart diseases nor electrocardiographic abnormalities at baseline. Among them, we identified 131 VPC cases using standard 12-lead ECG and classified them into left bundle branch block (LBBB) type (n = 74), right bundle branch block (RBBB) type (n = 21), and undetermined type (n = 36) according to their morphology. These subjects were followed up until December 2008; we compared all-cause, cardiac and coronary heart disease (CHD) mortality rates using multivariate Cox regression analysis between those with and without VPC.Results: No VPCs were associated with all-cause and cardiac mortality, but the LBBB type was significantly associated with CHD mortality (hazard ratio, 2.73; 95% confidence interval, 1.11-6.73) after controlling for age, sex, smoking status, alcohol consumption, and underlying diseases.Conclusions: Among Japanese atomic bomb survivors without obvious heart diseases, LBBB-type VPC was associated with increased CHD mortality. Larger studies are needed to confirm the effect of morphology as it might help to predict the risk. [ABSTRACT FROM AUTHOR]

Aim We evaluated the effect of pimobendan, a positive inotropic agent, in elderly patients with frequent readmission as a result of heart failure despite conventional therapy. Methods Pimobendan was given to five male patients with severe chronic heart failure ( New York Heart Association class III- IV) (age range 69-89 years; mean 78 ± 8 years; ischemic cardiomyopathy in three cases, dilated cardiomyopathy in two cases) who required repeated admission for heart failure despite conventional therapy with angiotensin inhibitors, beta-blockers, diuretics and anti-arrhythmic agents. After the addition of pimobendan at a dose of 1.25-3.75 mg/day, we evaluated serum levels of brain natriuretic peptide ( BNP), left ventricular ejection fraction ( LVEF), septal e′ and left ventricular end-diastolic diameter ( LVDD) by echocardiography, as well as readmission rates for more than 2 years. Results The serum level of BNP significantly decreased after treatment with pimobendan, although its level returned to pretreatment levels after 2 years. LVEF significantly improved after the treatment, with the improvement continuing beyond the 2 years, although LVDD did not change after treatment. Septal e′ significantly improved after the treatment, although its level returned to pretreatment levels at 2 years after the treatment. Readmission rates significantly decreased for 2 years after the treatment, although one patient required cardiac resynchronization therapy for severe heart failure, and another patient required cardiac pacemaker implantation for sick sinus syndrome 2 years after adding pimobendan. Conclusions Pimobendan in conjunction with conventional therapy for heart failure decreases the readmission rate in elderly patients with severe heart failure for at least 2 years. Geriatr Gerontol Int 2014; 14: 109-114. [ABSTRACT FROM AUTHOR]

Melatonin is well known to have a beneficial effect on the cardiovascular system, but it remains to be elucidated whether melatonin has a therapeutic effect on the vascular damage induced by the potential vasoactive substance angiotensin II ( Ang II). In this study, the effects of melatonin on Ang II-induced vascular endothelial damage were investigated. In cultured vascular endothelial cells, Ang II stimulation increased ROS generation and inhibited eNOS phosphorylation ( Ser1177), both of which were clearly restored by pretreatment with melatonin. The translocation of p47 phox subunit of NADPH oxidase from the cytosol to plasma membrane was promoted in Ang II-treated vascular endothelial cells, which was canceled by melatonin pretreatment. In Ang II-infused rats, increased ROS generation in the aortic wall and impaired endothelial function of the aortic ring were observed, which were rescued by coadministration of melatonin. In vasculature, melatonin receptor agonist ramelteon had the antioxidative effect in the same manner as melatonin by itself. These findings suggest that melatonin directly ameliorates Ang II-induced vascular endothelial damage partly via its antioxidative properties, providing with us the potential rationale for clinical application of melatonin to the prevention from cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] VEGF-A upregulates sVEGFR-1 expression in human vascular endothelial cells. [•] VEGF-A does not affect the expression of full-length VEGFR-1. [•] VEGF-A-elicited induction of sVEGFR-1 is mediated through VEGFR-2-MEK-PKC signaling. [•] VEGF-A may regulate the alternative splicing of the VEGFR-1 gene. [ABSTRACT FROM AUTHOR]

A 72-year-old woman with sick sinus syndrome (SSS), who had frequent paroxysmal atrial fibrillations (PAfs) and normal cardiac function, was admitted to our hospital due to syncope. PAfs frequently occurred during the first week after DDD pacemaker implantation (PMI), with closed loop stimulation (CLS) rate-adaptive mode off, but were completely suppressed during the second week, with CLS on, and had been well-controlled over three years thereafter. However, PAfs occasionally occurred under intense sympathetic activity during 6 months after PMI as well, and were effectively terminated by disopyramide which had anticholinergic effect. Thus, the development and maintenance of PAf were thought to be associated with destabilized cardiac autonomic activities, that is, sympathetic and parasympathetic dominance, respectively. Additionally, heart rate variability analyses after implementation of CLS revealed the restoration of sympathetic and parasympathetic components. Accordingly, CLS mode was considered to play a critical role in preventing PAf by reflecting autonomic activity in heart rhythm in this SSS patient. [Copyright &y& Elsevier]

ABSTRACT The importance of treating non‐pulmonary vein (PV) foci is increasing with improvements in the durability of PV isolation. We describe two cases wherein non‐PV foci were induced by mechanical irritation and conventional induction in the same area, which was impossible to induce after ablation, suggesting a relationship between mechanical irritation and induction of non‐PV foci. In a recurrent case of non‐PV foci, atrial fibrillation (AF) was induced only by mechanical irritation. No recurrence has been observed since the ablation of the area. Thus, treatment of the AF induction site with mechanical irritation could be considered an effective therapy for non‐PV foci. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 86-year-old woman was admitted to Nagasaki University Hospital, Nagasaki, Japan, due to repetitive syncope with convulsions. She was admitted for dementia and frailty, and she had been treated for paroxysmal supraventricular tachycardia (PSVT) due to type A Wolff–Parkinson–White syndrome and essential hypertension.

The article presents a case study of a 65-year-old Japanese woman who was taken to the hospital after developed chest discomfort during exercise. It mentions that her past medical history included chronic thyroiditis at 61 years-of-age, and states that electrocardiography shows her heart and respiratory sounds normal. It also mentions that results of coronary angiography and left ventriculography were normal.

The article focuses on a case study of an 83-year-old Japanese woman with heart failure who had been medicated with prednisolone to treat myalgia rheumatica and a rivastigmine transdermal patch for dementia with Lewy bodies (DLB) upon admission to Nagasaki Rosai Hospital in Nagasaki, Japan. It discusses the occurrence of sinus arrest at day 9 after admission, the common adverse effects of acetylcholinesterase inhibitors and the patient's autonomic dysfunction.

Background Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects. Clinical Trial Registration www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409.

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

Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known., Methods and Results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P =0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P =0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P =0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P =0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed., Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification., Clinical Trial Registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)