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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Peripheral arterial disease (PAD) is a phenotype of atherosclerotic disease often associated with cerebrovascular or coronary artery disease. The incidence of cardiovascular events in patients with PAD is 5.4% per year, which is higher than that of cerebrovascular or coronary artery disease. The most useful screening method for PAD is the ankle brachial pressure index (ABI). The ABI should be measured in (1) all patients with lower limb symptoms such as claudication, (2) all patients aged 65 years and over, and (3) those aged 50 to 65 years who have risk factors such as smoking and diabetes mellitus. PAD is diagnosed if the ABI is

Diastolic mitral regurgitation is a type of functional mitral regurgitation that develops via a reversal of the left atrioventricular pressure gradient during diastole. This study aimed to explore the mechanism underlying early diastolic mitral regurgitation (EDMR) in patients with left ventricular (LV) aneurysms after anterior myocardial infarction (AMI) by assessing the intraventricular pressure difference using vector flow mapping. We enrolled 23 consecutive patients with LV aneurysms (with and without EDMR) and 15 healthy men as controls. In the control group, LV suction began from the apex during early diastole. In contrast, the blood that pooled in the apical aneurysm during systole generated a relatively higher pressure at the apex than at the basal LV during early diastole; consequently, the pressure reversal phenomenon occurred in the LV. Compared to the EDMR– group, the EDMR + group (n = 7) exhibited a significantly higher diastolic time ratio ([time from the second heart sound to the pressure inversion point]/[total diastolic time]) (P

Background Sedentary behavior may be an independent risk factor for cardiovascular events. This study aimed to clarify the effects of extended sedentary time in patients with diabetic kidney disease (DKD) on the risk of all-cause death and new events.Methods and Results:A prospective cohort study was performed over 39 months. The study included 173 patients with DKD who completed the International Physical Activity Questionnaire (IPAQ) (101 men; mean age, 71±11 years); 37 patients (21.4%) were diagnosed with cardiovascular disease (CVD). New events were defined as all-cause death, cerebral stroke, or CVD requiring hospitalization or commencing hemodialysis (HD). Data were analyzed using a multivariate Cox proportional hazard regression model with variables, including sedentary time. There were 34 cases of new events during the observation period, including 4 cases of stroke, 20 cases of CVD, 4 cases of HD implementation, and 6 cases of death. Hazard ratio (HR) calculations for the new event onset group identified sedentary time as a significant independent variable. The independent variable that was identified as a significant predictor of new events was the sedentary time (60 min/day; HR: 1.23, 95% CI: 1.05-1.45, P=0.012). Conclusions Extended sedentary time increased the risk of new cardiovascular or renal events and/or all-cause death in patients with DKD.

Background There is an increasing number of elderly patients with pulmonary arterial hypertension (PAH), and their characteristics differ from those of young or middle-aged patients with this condition. Case summary A 73-year-old woman with a history of myocardial infarction and cardiovascular risk factors was admitted to the hospital with 2-week exertional dyspnoea. Her initial diagnosis was heart failure with preserved ejection fraction, but the symptoms persisted despite receiving treatment with diuretics. Additional tests showed a significant decrease in diffusing capacity of carbon monoxide and findings suggestive of severe pulmonary hypertension (PH). Contrast-enhanced computed tomography of the chest, and pulmonary angiography, showed no narrowing or obstruction of the pulmonary arteries. Right heart catheterization revealed haemodynamic data implying pre-capillary PH. Her condition gradually deteriorated to World Health Organization functional class IV, and sequential combination therapy with tadalafil, macitentan, and selexipag was initiated with a PAH diagnosis; however, she died 1 month later. Pathological findings in autopsy were consistent with PAH, and some parts of the lungs revealed the presence of obstructive and interstitial lung disease. Discussion The majority of elderly patients with PAH might have multimorbidity. However, there is no specific treatment strategy. It is associated with diagnostic delay and worse prognosis; therefore, early suspicion and comprehensive tests, including right heart catheterization, are essential for better management.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition in which an organic thrombus remains in the pulmonary artery (PA) even after receiving anticoagulation therapy for more than 3 months and is complicated by pulmonary hypertension (PH), leading to right-sided heart failure and death. CTEPH is a progressive pulmonary vascular disease with a poor prognosis if left untreated. The standard treatment for CTEPH is pulmonary endarterectomy (PEA), which is usually performed only in specialized centers. In recent years, balloon pulmonary angioplasty (BPA) and drug therapy for CTEPH have also shown good results. This review discusses the complex pathogenesis of CTEPH and presents the standard of care, PEA, as well as a new device called BPA, which is showing remarkable progress in efficacy and safety. Additionally, several drugs are now demonstrating established evidence of efficacy in treating CTEPH.

Decreased physical activity and activities of daily living (ADL) in patients on hemodialysis (HD) are associated with a poor prognosis. Additionally, comorbid peripheral arterial disease is associated with further deterioration. We conducted a cross-sectional study of ADL difficulty and life-space assessment (LSA) in three groups of patients on hemodialysis according to their ankle-brachial index (ABI) values. The 164 patients were divided into ABI Low (ABI < 0.9), Normal (0.9 ≤ ABI < 1.3), and High (1.3 ≤ ABI) groups, and compared using analysis of covariance with LSA and ADL difficulty adjusted for age. The Kihon checklist (KCL) was used to assess the presence of frailty. The LSA was lower in the Low group than in the High group (F = 3.192, p = 0.044). Similarly, the ADL difficulty was significantly lower in the Low group than in the Normal group (F = 3.659, p = 0.028). In the Low group, the proportion of patients with frailty was 47.1% and KCL physical was significantly lower, indicating that patients on HD with a lower ABI had a higher prevalence of frailty and lower LSA and ADL difficulty. In conclusion, patients on HD with decreased ABI values most likely exhibit decline in physical activity and ADL due to frailty and claudication.

BackgroundReduced lower limb circumference due to sarcopenia in patients with type 2 diabetes mellitus (T2DM) could be a useful screening tool for arteriosclerosis. Hence, the objective of this study was to clarify the relation between lower limb circumference and other body composition factors, muscle strength, and patient characteristics,and the progression of arteriosclerosis in patients with T2DM. MethodsWe included114 patients with T2DM receiving outpatient care, and assessed body composition (lower limb circumferences including tibial rough surface-calf 26% [TRSC%]), muscle strength indicators, patient characteristics, clinical diabetic neuropathy status, and examined their associations with brachial–ankle pulse wave velocity (ba-PWV) using multiple regression analysis. Additionally, the severity of ba-PWV was classified into 1400 cm/s, 1650 cm/s, and 1963 cm/s to investigate their associations using logistic regression analysis. ResultsThe mean age was 63.12±11.96 years and participants had T2DM for 11.25±9.45 years. Body mass index (BMI), HbA1c, abnormal ankle reflex, and TRSC% were adopted in the multiple regression analysis with ba-PWV as the dependent variable. In the logistic regression analysis of ba-PWV divided by 1400 cm/s, an index of arteriosclerosis, BMI was adopted, and when divided by 1963 cm/s, a mortality risk index, BMI, abnormal ankle reflex, and TRSC% were adopted.ConclusionArteriosclerosis in patients with T2DM is associated with a decrease in lower limb circumference; TRSC% was independently associated with severe arteriosclerosis when ba-PWV was ≥1963 cm/s, which is an indicator of mortality risk. Thus, lower limb circumference in the form of TRSC% may reflect the progression of arteriosclerosis.

Hemodialysis patients with diabetic kidney disease (DKD) experience blood glucose fluctuations owing to insulin removal. We evaluated the effects of single and long-term application of neuromuscular electrical stimulation (NMES) during hemodialysis on glycemic control. This trial was conducted in two stages: Stage 1, following a crossover design and 4 week washout period, eleven outpatients with DKD either underwent a single bout of NMES for 30 min (NMES period) or rested (control period) after receiving nutritional support during hemodialysis; Stage 2, following a crossover design and 4 week washout period, each participant received the intervention for 12 weeks. NMES was administered for 30 min at the maximum tolerable intensity. The mean subcutaneous glucose concentration and mean amplitude of glycemic excursion (MAGE) were determined by flash glucose monitoring for 24 h. Changes in glycoalbumin and MAGE before and after NMES initiation were evaluated. The mean blood glucose level and MAGE after a single bout of NMES were significantly lower than those after rest. Glycoalbumin levels and echo intensity of the rectus femoris tended to decrease, but not significantly by ANOVA due to a lack in statistical power after the dropout of three patients. NMES in end-stage DKD decreased blood glucose levels during and after hemodialysis.

Introduction and Hypothesis: White blood cell (WBC) count in healthy persons is reported to be associated with the risk of coronary artery disease (CAD) and all-cause death. The aim of our study was to determine whether WBC count predicts cardiovascular outcome, including heart failure and mortality, in consecutively registered patients with type 2 diabetes. Methods and Results: This was a post-hoc study from the Intensive Lipid and Blood Pressure Lowering and Cardiovascular Outcome Randomized Controlled Trial in Patients with CAD and type 2 diabetes. A total of 7,608 participants (mean age 68 years, 72% men) had WBC measured at baseline and were eligible for this study. Participants were followed for a mean of 1,328 days. We used Cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI). Participants with WBC count in the highest quartile had an adjusted HR for all-cause death of 1.66 (95% CI, 1.33 to 2.06, Figure) compared to those in the lowest quartile (WBC Conclusions: In patients with CAD and type 2 diabetes, higher WBC count may have potential as a predictor for all-cause death, myocardial infarction, and heart failure but not stroke. Disclosure A. Kawabe: None. Y. Nakatani: None. S. Ono: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. T. Yasu: None.

The association of gestational hypertension (GH) with future hypertension in Japanese women is unclear. Hence, this study aimed to examine the association between GH and the risk of future hypertension in middle-aged-to-older Japanese women. A case-control study was performed, including 62 hypertensive women (case) and 75 nonhypertensive women (control). GH during the first pregnancy was diagnosed on the basis of the Maternal and Child Health Handbook record. Hypertensive women were recruited from outpatients in the hospital and residents who completed an annual health check-up in a community. Hypertension was defined as blood pressure with systolic blood pressure &ge, 140 mmHg and/or diastolic blood pressure &ge, 90 mmHg, or taking antihypertensive medications. The average age (SD) of the cases and controls at the time of recruitment was 63.1 (8.4) and 57.7 (9.4), respectively. The multivariable-adjusted odds ratio of GH for hypertension in middle-aged-to-older women was 4.2 (95% confidence interval, 1.0&ndash, 17.5) after adjustment for potential confounding factors such as age and body-mass index (BMI) upon recruitment, prepregnancy BMI, and age at first delivery. In conclusion, GH can be an independent risk factor for future hypertension among Japanese women.

Introduction: Hemorheology (blood viscosity) was reported to be a strong predictor of cardiovascular events in the Edinburgh Artery Study. However, deterioration in hemorheology through microvessels is a potential adverse effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. This study aimed to clarify the effect of dapagliflozin on blood fluidity. Method: This multi-center, open-label, randomized, comparative study included 90 patients with type 2 diabetes mellitu. Patients were randomly divided into treatment groups with and without dapagliflozin treatment, and each item was investigated. The primary endpoint was the whole blood transit time, based on the difference from the baseline to 16 weeks after enrollment, as measured by a microchannel array flow analyzer (MC-FAN). To assess this outcome, a 15% noninferiority margin (clinically significant cut-off value) was used. To test the noninferiority of the treatment, a t-distribution was used to calculate the 95% confidence interval to assess the difference from the baseline. Results: The whole blood transit time in the dapagliflozin group was 41.8 ± 6.1 sec (mean ± SD) before administration, and 43.4 ± 6.8 sec at 16 weeks after dapagliflozin administration. In the control group, the whole blood transit time was 40.5 ± 3.0 sec before administration and 39.9 ± 3.8 sec after 16 weeks. The difference between groups from the baseline to 16 weeks after enrollment was 1.7 sec [0.2, 3.5] (95% C.I), confirming the noninferiority of dapagliflozin administration. Futher, the analysis Results of the differences between groups according to the some items (the baseline of hematocrit, HbA1c levels and the whole blood transit time) for baseline, demonstrating the noninferiority of dapagliflozin administration in these items. Conclusion: Dapagliflozin was unlikely to have negative effects on blood fluidity after administration irrespective of the baseline Hematocrit, HbA1c levels and the whole blood transit time. Disclosure S. Ono: None. Y. Nakatani: None. A. Kawabe: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. Y. Aso: None. T. Yasu: None. Funding AstraZeneca

重症虚血肢の外科的血行再建に際し，大伏在静脈が不良である場合にバイパスグラフト選択に苦慮することが多いが，我々は浅大腿動脈に遠隔血栓内膜摘除術（remote endarterectomy；RE）を行うことによりグラフト長補填が可能であった症例を経験したので報告する．症例は72 歳男性．右第一趾の爪下膿瘍を伴った下肢虚血で当科紹介となった．大腿部大伏在静脈は分岐が多く性状は不良であったため，右浅大腿動脈にremote RE を行い，その末梢側をin-flow としたin-situ バイパスを後脛骨動脈に行った．術後足趾の感染は治癒し，跛行症状も改善した．, Bypass graft selection for surgical revascularization of critical limb ischemia is often difficult in cases where the great saphenous vein is inadequate. Herein, we report a case where we performed remote superficial femoral artery（SFA）endarterectomy, by which we adjusted thegraft length. A 72-year-old man with lower limb ischemia accompanied by subungual abscess on the right first toe was referred to our department. As the femoral great saphenous vein had many branches and its condition was poor, we performed remote right SFA endarterectomy followedby an in situ bypass to the posterior tibial artery, in which the distal side was used as an in-flow site. After the surgery, infection of the toe healed and the claudication improved.

Background Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells. Conclusions Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.

This study evaluated the effects of a glucagon-like peptide-1 receptor agonist on gastrointestinal (GI) tract motility and residue rates by examining GI transit time and lumen using capsule endoscopy.GI motility and lumen were assessed by capsule endoscopy before and after liraglutide administration in 14 patients with type 2 diabetes mellitus (T2DM).Gastric transit time in the group with diabetic neuropathy (DN) was 1:12:36±1:04:30h before liraglutide administration and 0:48:40±0:32:52h after administration (nonsignificant difference, P=0.19). Gastric transit time in the non-DN group was 1:01:30±0:52:59h before administration and 2:33:29±1:37:24h after administration (significant increase, P=0.03). Duodenal and small intestine transit time in the DN group was 4:10:34±0:25:54h before and 6:38:42±3:52:42h after administration (not significant, P=0.09) and, in the non-DN group, 3:51:03±0:53:47h before and 6:45:31±2:41:36h after administration (significant increase, P=0.03). The GI residue rate in the DN group was 32.1±24% before administration and 90.0±9.1% after administration (significant increase, P0.001), and increased in all patients; in the non-DN group, it was 32.1±35.3% before and 78.3±23.9% after administration (significant increase, P0.001), and also increased in all patients.Liraglutide causes delayed gastric emptying and inhibits duodenal and small intestine motility. However, these GI movement-inhibiting effects may be decreased or absent in patients with DN-associated dysautonomia.

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34+/133+ cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner–Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient’s preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34+/133+ cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

A right-sided aortic arch is normally asymptomatic. We report the case of an 84-year-old man with right internal jugular vein thrombosis caused by an aneurysm in a right-sided aortic arch. The patient had undergone open repair of an abdominal aortic aneurysm and had an uneventful postoperative course. However, a routine postoperative contrast-enhanced thoracic and abdominal computed tomography scan showed right internal jugular vein thrombosis. The patient had no history of catheter insertion in the right jugular veins and had no hereditary coagulopathy. It was presumed that the cause of this thrombosis was compression of the right brachiocephalic vein by an aneurysm of the right-sided ascending aorta that was considered too small to require surgical repair. The right internal jugular vein thrombosis was successfully treated with edoxaban.

Coronary spastic angina (CSA) is relatively more common in young people than in elderly people. Here, we present three cases of elderly male patients who experienced out-of-hospital cardiac arrest (OHCA) likely due to coronary spasm-induced ventricular fibrillation (Vf) from 2013 to 2016. After defibrillation, emergency coronary arteriography demonstrated severe coronary vasospasm that resolved following intracoronary infusion of nitroglycerin in the right coronary arteries in all three patients, with no organic obstructive lesion in the coronary arteries after nitroglycerin infusion. Case 1 was a 74-year-old patient with a past history of unstable angina and no organic obstructive lesion on coronary arteriography. He was administered oral amlodipine, isosorbide mononitrate, and nicorandil. He survived an OHCA and underwent implantable cardioverter defibrillator (ICD) implantation on day 57. Case 2 was a 71-year-old patient without prior CSA, who suddenly lost consciousness during a break after tennis. Vf was reversed to sinus rhythm by defibrillation in the ambulance. He died of multi-organ failure on day 7. Case 3 was a 66-year-old patient diagnosed with multi-vessel CSA by coronary arteriography with acetylcholine provocation test. He survived an OHCA associated with inferior acute myocardial infarction, rejected ICD implantation, and has not had a chest pain attack or syncope since discharge. .

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34+/133+ cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner–Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient’s preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34+/133+ cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

Introduction: Although the prognostic efficacy of out-patient cardiac rehabilitation (OPCR) in patients with coronary artery disease (CAD) has been established in Western countries, it has not been studied in Japan, where both incidence and mortality of CAD are known to be much lower than in Western counties. Methods: To determine the prognostic efficacy of OPCR in Japan, a prospective, controlled, multicenter study of OPCR (J-REHAB) was conducted in 15 hospitals in Japan. A total of 1047 patients hospitalized with cardiac events were prospectively assigned to either OPCR group (n=848) or Non-OPCR group (n=199) according to patient’s preference at the time of hospital discharge. Patients in OPCR group were scheduled to participate in a comprehensive OPCR program for 3 months and Non-OPCR group received usual care. Event-free survivals for cardiac and all-cause death/rehospitalization were assessed according to the initial group assignment and the “prespecified” actual OPCR performance (attendance >=4 times/month and total exercise time >=150 min/week). Results: Patients were followed-up for 416days on average and the follow-up rate was 99.4%. At baseline, patients were 64±11years of age, 85% was male, 58% acute myocardial infarction, with preserved EF (53±13%). By Kaplan-Meier analysis, OPCR group had significantly better event-free survival for cardiac death/rehospitalization (p Conclusions: The first Japanese prospective multicenter J-REHAB study has demonstrated that active participation in OPCR is associated with better event-free survival in CAD patients, independent of baseline clinical characteristics.

Long- and short-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) liraglutide and lixisenatide, which are available for diabetes therapy, may act on the autonomic nervous system to increase heart rate (1,2). We performed a prospective, single-center, randomized, open-label study with a 1:1 allocation ratio using a 24-h Holter electrocardiogram to compare the effects of these GLP-1RAs on the autonomic nervous system. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients participating in this study. The study is registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000017770). Sixty patients with type 2 diabetes who were admitted for diabetes treatment and had not received dipeptidyl peptidase-4 inhibitors or GLP-1RAs were randomly divided into a liraglutide (age 64.9 ± 12.7 years, HbA1c 10.3 ± 2.5% [89.1 mmol/mol], BMI 24.6 ± 4.8 kg/m2, diabetes duration 7.8 ± 7.8 years) or …