Delivery catheter system carries more physiological right ventricular septal pacing than stylet system.

INTRODUCTION: The Mt. FUJI multicenter trial demonstrated that a delivery catheter system had a higher rate of successful right ventricular (RV) lead deployment on the RV septum (RVS) than a conventional stylet system. In this subanalysis of the Mt. FUJI trial, we assessed the differences in electrocardiogram (ECG) parameters during RV pacing between a delivery catheter system and a stylet system and their associations with the lead tip positions. METHODS: Among 70 patients enrolled in the Mt FUJI trial, ECG parameters, RV lead tip positions, and lead depth inside the septum assessed by computed tomography were compared between the catheter group (n = 36) and stylet group (n = 34). RESULTS: The paced QRS duration (QRS-d), corrected paced QT (QTc), and JT interval (JTc) were significantly shorter in the catheter group than in the stylet group (QRS-d: 130 ± 19 vs. 142 ± 15 ms, p = .004; QTc: 476 ± 25 vs. 514 ± 20 ms, p < .001; JTc: 347 ± 24 vs. 372 ± 17 ms, p < .001). This superiority of the catheter group was maintained in a subgroup analysis of patients with an RV lead tip position at the septum. The lead depth inside the septum was greater in the catheter group than in the stylet group, and there was a significant negative correlation between the paced QRS-d and the lead depth. CONCLUSION: Using a delivery catheter system carries more physiological depolarization and repolarization during RVS pacing and deeper screw penetration in the septum in comparison to conventional stylet system. The lead depth could have a more impact on the ECG parameters rather than the type of pacing lead.

Clinical impact of cryoballoon posterior wall isolation using the cross-over technique in persistent atrial fibrillation.

BACKGROUND AND AIMS: Successful left atrial posterior wall isolation (LAPWI) using only the cryoballoon (CB) is technically challenging for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy of the cross-over technique, wherein an overlapped ablation is performed by placing the CB from both directions in contact with the LAPW. METHODS: This was a single-center, retrospective, observational study of 194 consecutive patients with persistent atrial fibrillation (PerAF) who underwent a first-time procedure of pulmonary vein isolation (PVI) + PWI (108 patients) or PVI-only (86 patients) using the CB. The cross-over technique was applied in all LAPWI. RESULTS: For ablation of the LA roof and bottom, respectively, a mean of 8.6 ± 1.0 (right to left [R→L] 4.3 ± 1.1 and left to right [L→R] 4.3 ± 1.1) and 9.1 ± 1.2 (R→L 4.6 ± 1.6 and L→R 4.5 ± 1.2) CB applications were delivered. LAPW was successfully isolated solely using the CB in 99.1% of patients. Although the PVI + PWI group had significantly longer procedure time, no severe adverse events were observed in either group. During a median follow-up of 19 months, freedom from recurrence of all atrial tachyarrhythmias was achieved in 93.5% of the PVI + PWI group and 72.9% of the PVI-only group (p = .011). CONCLUSIONS: LAPWI performed solely with the CB using the cross-over technique is feasibly, safe, and was independently associated with a significantly higher freedom from recurrence of atrial tachyarrhythmias compared with PVI alone in patients with PerAF.

Usefulness of delivery catheter on accurate right ventricular septal pacing: Mt FUJI trial.

AIMS: Although the delivery catheter system for pacemaker-lead implantation is a new alternative to the stylet system, no randomized controlled trial has addressed the difference in right ventricular (RV) lead placement accuracy to the septum between the stylet and the delivery catheter systems. This multicentre prospective randomized controlled trial aimed to prove the efficacy of the delivery catheter system for accurate delivery of RV lead to the septum. METHODS AND RESULTS: In this trial, 70 patients (mean age 78 ± 11 years; 30 men) with pacemaker indications of atrioventricular block were randomized to the delivery catheter or the stylet groups. Right ventricular lead tip positions were assessed using cardiac computed tomography within 4 weeks of pacemaker implantation. Lead tip positions were classified into RV septum, anterior/posterior edge of the RV septal wall, and RV free wall. The primary endpoint was the success rate of RV lead tip placement to the RV septum. RESULTS: Right ventricular leads were implanted as per allocation in all patients. The delivery catheter group had higher success rate of RV lead deployment to the septum (78 vs. 50%; P = 0.024) and narrower paced QRS width (130 ± 19 vs. 142 ± 15 ms P = 0.004) than those in the stylet group. However, there was no significant difference in procedure time [91 (IQR 68-119) vs. 85 (59-118) min; P = 0.488] or the incidence of RV lead dislodgment (0 vs. 3%; P = 0.486). CONCLUSION: The delivery catheter system can achieve a higher success rate of RV lead placement to the RV septum and narrower paced QRS width than the stylet system. TRIAL REGISTRATION NUMBER: jRCTs042200014 (https://jrct.niph.go.jp/en-latest-detail/jRCTs042200014).

Low coenzyme Q10 levels in patients with acute cardiovascular disease are associated with long-term mortality.

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention.

BACKGROUND: Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG level on cardiovascular events has not been fully investigated. METHODS: We enrolled 240 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1 year. We excluded patients with a history of acute coronary syndrome, advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), or uncontrolled diabetes mellitus (HbA1c ≥7.0 %). Fasting blood glucose (FBS), HbA1c, and 1,5-AG levels were measured prior to PCI and at the time of follow-up angiography. Clinical events, including target lesion revascularization, target vessel revascularization, and revascularization of new lesions, were evaluated. RESULTS: Subjects were divided into two groups according to clinical outcomes: the Event (+) group (n = 40) and the Event (-) group (n = 200). No significant differences were observed, except for the number of diseased vessels and the prevalence of statin use, in baseline clinical characteristics between the two groups. Serum levels of 1,5-AG at follow-up were significantly lower in the Event (+) group than in the Event (-) group (P = 0.02). A significant reduction in 1,5-AG level from baseline to follow-up was observed in the Event (+) group compared with the Event (-) group (P = 0.04). The association between 1,5-AG levels at follow-up and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P = 0.04). CONCLUSIONS: Low and exacerbated levels of 1,5-AG were associated with cardiovascular events in the present study, indicating that postprandial hyperglycemia is an important risk factor for adverse clinical events even in patients with HbA1c < 7.0 %, following first-time elective PCI.

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation.

BACKGROUND: Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-ß, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. CONCLUSIONS: Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

Mid-term outcomes of delivery catheter-based and stylet-based right ventricular septal pacing: Follow-up results from a multicenter, prospective, randomized study.

Background: The Mt FUJI study was a multicenter, prospective, randomized, single-blind, controlled trial comparing delivery catheter-based and stylet-based right ventricular (RV) lead placement at the RV septum. This study extended the follow-up duration to 1 year after implantation. Methods: Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid-term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events. Results: At the 1-year follow-up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [-11.1, 26.5] pg/mL vs. -8.7 [-15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p < .001). All-cause death, hospitalization for heart failure, new development of atrial fibrillation, and pacing-induced cardiomyopathy occurred in seven patients in the delivery catheter group and five in the stylet group. Conclusion: The delivery catheter system was similarly useful and safe compared to the stylet system in the mid-term follow-up from the Mt FUJI trial. Further long-term evaluations are warranted.

Accumulation of polyunsaturated fatty acid-derived metabolites in the sarcopenic muscle of aging mice.

AIM: Although it is known that advanced age alters skeletal muscle lipid metabolism, the role(s) of polyunsaturated fatty acid-derived metabolites (mostly eicosanoids and docosanoids) in sarcopenia are not clear. We therefore examined the changes in the metabolites of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in the sarcopenic muscle of aged mice. METHODS: We used 6- and 24-month-old male C57BL/6J mice as healthy and sarcopenic muscle models, respectively. Skeletal muscles were removed from the lower limb and subjected to a liquid chromatography-tandem mass spectrometry analysis. RESULTS: The liquid chromatography-tandem mass spectrometry analysis detected distinct changes of metabolites in the muscles of the aged mice. Of the 63 metabolites identified, nine were significantly higher in the sarcopenic muscle of aged mice compared with the healthy muscle of young mice. In particular, prostaglandin E2 , prostaglandin F2a , thromboxane B2 , 5-hydroxyeicosatetraenoic acid, and 15-oxo-eicosatetraenoic acid (arachidonic acid-derived metabolites), 12-hydroxy-eicosapentaenoic acid and 14,15-epoxy-eicosatetraenoic acid (eicosapentaenoic acid-derived metabolites) and 10-hydroxydocosa-hexaenoic acid and 14-hydroxyoctadeca-pentaenoic acid (docosahexaenoic acid-derived metabolites) were significantly higher in aged tissue compared with young tissue (all P < 0.05). CONCLUSIONS: We observed the accumulation of metabolites in the sarcopenic muscle of aged mice. Our results may provide new insights into the pathogenesis and progression of aging- or disease-related sarcopenia. Geriatr Gerontol Int 2023; 23: 297-303.

A Case of Floating Aortic Arch Thrombosis in a Patient without Thrombophilia.

Floating aortic arch thrombi-blood clots forming in an aorta without aneurysms or atherosclerosis-in a normal aorta are exceedingly rare. The etiology is unknown, and there are no guidelines for appropriate treatment strategies. We report a case of floating aortic arch thrombosis in a patient without coagulopathy that was treated surgically. As the mass could not be identified preoperatively as a tumor or thrombus, synthetic graft replacement was performed, allowing resection of the lesion site. Histopathological examination revealed erosion and fissures in the tunica intima of the aorta, which suggested vessel damage to the tunica intima as the cause.

Successful implantation of a leadless pacemaker in a patient with complete atrioventricular block and congenital absence of superior vena cava: a case report.

BACKGROUND: Congenital absence of superior vena cava (CASVC) is an extremely rare vascular anomaly often associated with conduction disturbances which makes implantation of a pacemaker difficult. We report a case of pacemaker implantation in a patient presenting with complete atrioventricular block (c-AVB) with bilateral absence of the SVC. CASE SUMMARY: A 68-year-old man who had experienced dyspnoea on exertion by c-AVB was admitted to our hospital for treatment and management. Permanent pacemaker insertion was initially planned; however, an endocardial pacemaker lead could not be implanted in the right atrium. Computed tomography scan with contrast revealed that the venous blood from the upper half of the body flowed into the inferior vena cava via the azygos vein. Due to the difficulty of inserting an endocardial lead from the subclavian vein, a leadless pacemaker (LP) was implanted instead via the femoral vein. DISCUSSION: This is the first case of an LP implantation in a patient presenting with c-AVB with CASVC. Confirmation of blood vessel anatomy to rule out CASVC is necessary prior to pacemaker implantation when abnormal venous anatomy is suspected.

Comparison of delivery catheter-based and stylet-based right ventricular lead placement at the right ventricular septum under fluoroscopic guidance judged by cardiac CT (Mt. FUJI): a study protocol for the Mt. FUJI randomised controlled trial.

INTRODUCTION: Pacing-induced cardiomyopathy occasionally occurs in patients undergoing pacemaker implantation. Although compared with right ventricular (RV) apical pacing, RV septal pacing can attenuate left ventricular dyssynchrony; the success rate of lead placement on the RV septum using the stylet system is low. Additionally, no randomised controlled trial has addressed the issue regarding the accuracy of RV lead placement on the RV septum using the stylet and delivery catheter systems. This study hypothesises that a newly available delivery catheter system can improve the accuracy of RV lead placement on the RV septum. METHODS AND ANALYSIS: In a multicentre, prospective, randomised, single-blind, controlled trial, 70 patients with pacemaker indication owing to atrioventricular block will be randomised to either the delivery catheter or stylet group before the pacemaker implantation procedure. The position of the RV lead tip will be assessed using ECG-gated cardiac CT in all patients within 4 weeks after pacemaker implantation. Lead tip positions are classified into three groups: (1) RV septum, (2) anterior/posterior edge of the RV septal wall and (3) RV free wall. The primary endpoint will be the success rate of RV lead tip placement on the RV septum, which will be evaluated using cardiac CT. ETHICS AND DISSEMINATION: This study will be conducted according to the stipulations of the Helsinki Declaration and the institutional review board of Hamamatsu University School of Medicine. The results of the study will be disseminated at several research conferences and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: jRCTs042200014; Pre-results.

The association between impairment of HDL cholesterol efflux capacity and atrial remodeling in atrial fibrillation.

This cross-sectional study enrolled 202 patients with atrial fibrillation (AF) who had undergone catheter ablation and evaluated the association between high-density lipoprotein (HDL) functionality, cholesterol efflux capacity (CEC) of HDL, and the pathophysiology of left atrial structural remodeling. Participants were divided into two groups, based on their left atrial volume index (LAVI) (< 34 mL/m2, n = 60 vs. LAVI ≥ 34 mL/m2, n = 142). We quantified three types of HDL CECs by the presence or absence of cyclic-AMP, as entire, and CEC dependent or not dependent on ATP binding cassette transporter A1 (ABCA1) and termed them Global CEC, ABCA1 CEC, and Non-ABCA1 CEC, respectively. Consequently, Global and Non-ABCA1 CECs were significantly impaired in patients with an enlarged LA (Global CEC: p = 0.039, Non-ABCA1 CEC: p = 0.022). Logistic regression analyses demonstrated that Non-ABCA1 CEC was significantly associated with an enlarged LA after adjusting for the conventional risk factors of AF. Furthermore, the association of higher Non-ABCA1 CEC with an enlarged LA was independent of serum levels of HDL cholesterol and serum myeloperoxidase (Odds ratio of 1 standard deviation higher: 0.64, 95% confidence interval: 0.43-0.95, p = 0.027). The findings of this study indicate the potential contribution of reduced Non-ABCA1 CEC in HDL to the pathophysiology in left atrial structural remodeling of patients with AF.

Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice.

AIM: We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. METHODS: We used 6-, 12- and 24-month (6 M, 12 M and 24 M)-old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real-time polymerase chain reaction, immunoblotting and histological analyses. RESULTS: The muscle weight and myocyte cross-sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4-hydroxy-2-nonenal and 3-nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC)-α, peroxisome proliferator-activated receptor gamma coactivator-1ß, sirtuin-1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin-proteasome pathway genes muscle ring finger-1 and atrogin-1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated-Akt and -p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). CONCLUSIONS: These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78-84.

Voluntary exercise and cardiac remodeling in a myocardial infarction model.

We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1ß, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

Correlation of Nutritional Indices on Admission to the Coronary Intensive Care Unit with the Development of Delirium.

BACKGROUND: Delirium is a common occurrence in patients admitted to the intensive care unit and is related to mortality and morbidity. Malnutrition is a predisposing factor for the development of delirium. Nevertheless, whether the nutritional status on admission anticipates the development of delirium in patients with acute cardiovascular diseases remains unknown. OBJECTIVE: This study aims to assess the correlation between the nutritional status on admission using the nutritional index and the development of delirium in the coronary intensive care unit. DESIGN: We examined 653 consecutive patients (mean age: 70 ± 14 years) admitted to the coronary intensive care unit of Juntendo University Hospital between January 2015 and December 2016. We evaluated three nutritional indices frequently used to assess the nutritional status, i.e., Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT). We defined delirium as patients with a delirium score >4 using the Intensive Care Delirium Screening Checklist. RESULTS: Delirium was present in 58 patients. All nutritional indices exhibited a tendency for malnutrition in the delirium group compared with the non-delirium group (GNRI, 86.5 ± 9.38 versus 91.6 ± 9.89; PNI, 36.4 ± 6.95 versus 41.6 ± 7.62; CONUT, 5.88 ± 3.00 versus 3.61 ± 2.56; for all, p < 0.001). Furthermore, the maximum delirium score increased progressively from the low- to the high-risk group, as evaluated by each nutritional index (GNRI, PNI, CONUT; for all, p < 0.001). A multivariate analysis revealed that the PNI and CONUT were independent risk factors for the occurrence of delirium. CONCLUSIONS: A marked correlation exists between the nutritional index on admission, especially PNI and CONUT, and the development of delirium in patients with acute cardiovascular diseases, suggesting that malnutrition assessment upon admission could help identify patients at high risk of developing delirium.

Possible Role of NADPH Oxidase 4 in Angiotensin II-Induced Muscle Wasting in Mice.

Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance. Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used. At baseline, there were no differences in physical characteristics between the WT and KO mice. Saline (vehicle, V) or AII was infused via osmotic minipumps for 4 weeks, after which, the WT + AII mice showed significant increases in Nox activity and NOX4 protein compared with the WT + V mice, as well as decreases in body weight, gastrocnemius muscle weight, and myocyte cross-sectional area. These changes were significantly attenuated in the KO + AII mice (27 ± 1 vs. 31 ± 1 g, 385 ± 3 vs. 438 ± 13 mg, and 1,330 ± 30 vs. 2281 ± 150 µm2, respectively, all P < 0.05). The expression levels of phospho-Akt decreased, whereas those of muscle RING Finger-1 (MuRF-1) and MAFbx/atrogin-1 significantly increased in the WT + AII mice compared with the WT + V mice. Furthermore, nuclear factor erythroid-derived 2-like 2 (Nrf2) and the expression levels of Nrf2-regulated genes significantly decreased in the WT + AII mice compared with the WT + V mice. These changes were significantly attenuated in the KO + AII mice (P < 0.05). Conclusion: Nox4 deficiency attenuated AII-induced muscle wasting, partially through the regulation of Nrf2. The Nox4-Nrf2 axis may play an important role in the development of AII-induced muscle wasting.

A proposal of clinical ECG index "vagal score" for determining the mechanism of paroxysmal atrioventricular block.

BACKGROUND: Paroxysmal atrioventricular block (P-AVB) is a well-known cause of syncope; however, its underlying mechanism is difficult to determine. This study aimed to evaluate a new ECG index, the "vagal score (VS)," to determine the mechanism of P-AVB. METHODS: We evaluated the VS in 20 patients with P-AVB (13 men, 7 women; aged 25-78 years [mean, 59.3 years]). The VS was developed by assigning 1 point each for the following: (1) no AVB or intraventricular conduction disturbance on the baseline ECG, (2) PR prolongation immediately before P-AVB, (3) sinus slowing immediately before P-AVB, (4) initiation of P-AVB by PP prolongation, (5) sinus slowing during ventricular asystole, and (6) resumption of AV conduction with PP shortening, and by assigning -1 point each for (7) the initiation of P-AVB by a premature beat, and (8) resumption of AV conduction by an escape beat. Based on the clinical situations and electrophysiologic findings, we considered the mechanism of P-AVB as vagally mediated or intrinsic conduction disease (ICD). RESULTS: The VS ranged from 5 to -2 points for each patient. Five patients with a definite vagally mediated P-AVB had high VSs (3-5 points). We observed characteristic ECG findings of ICD consisting of changes in AV conduction by an extrasystole and/or escape beat in only 5 of the 6 patients (83%) with a low VS (1 to -2). CONCLUSIONS: The VS is simple and potentially useful for determining the mechanism of P-AVB. P-AVB with a VS ≥3 strongly suggested a vagally mediated mechanism.

Significance of Serum Polyunsaturated Fatty Acid Level Imbalance in Patients with Acute Venous Thromboembolism.

AIM: Polyunsaturated fatty acids (PUFAs) take part in various biological events linked to the pathogenesis of venous thromboembolism (VTE), including inflammation, endothelial dysfunction, and hypercoagulability. Several studies have demonstrated the association between PUFAs and the occurrence of VTE. However, the role of PUFAs in the pathogenesis of VTE remains unclear. METHODS: We enrolled 45 patients with acute VTE and 37 age-, gender-, and body mass index-matched healthy volunteers to examine their PUFA levels. Serum omega 3 (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) and omega 6 (dihomogammalinolenic acid: DGLA and arachidonic acid: AA) fatty acids levels were measured within 24 h of admission. RESULTS: Patients with VTE showed significantly higher AA and lower EPA levels, and lower EPA/AA ratios than the controls. Multivariate analysis revealed that AA was an independent marker for VTE. In addition, we divided the patients based on their median age (58 years old). The younger patients with VTE showed significantly lower EPA/AA levels than their age-matched controls, whereas older patients with VTE showed a significantly higher AA/DGLA levels than the older controls. CONCLUSIONS: High serum AA levels and low EPA levels are associated with the development of acute VTE, suggesting that the imbalance of PUFAs may be a potential therapeutic target for preventing acute VTE.

Low Docosahexaenoic Acid, Dihomo-Gamma-Linolenic Acid, and Arachidonic Acid Levels Associated with Long-Term Mortality in Patients with Acute Decompensated Heart Failure in Different Nutritional Statuses.

The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 and March 2014. The association between long-term mortality, the geriatric nutritional risk index (GNRI), and levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) was investigated. The median age was 73 (64-82) years, and mortality was 29% (62 patients). The event-free survival rates for all-cause death were higher in patients with high PUFA levels or GNRI than in those with low PUFA levels or GNRI (p < 0.05 for all). In particular, high DGLA in the low-GNRI group and high DHA or AA in the high-GNRI group were associated with high event-free survival (p < 0.05 for all). After accounting for confounding variables, DHA, DGLA, and AA, but not EPA, were associated with long-term mortality (p < 0.01 for all). This study concludes that in patients with ADHF, decreased levels of DHA, DGLA, and AA are independently associated with long-term mortality in the various nutritional statuses.