Relationship between skin autofluorescence levels and clinical events in patients with heart failure undergoing cardiac rehabilitation.

BACKGROUND: Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. METHODS: This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. RESULTS: Patients' mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan-Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P < 0.05). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (odds ratio, 1.86; 95% confidence interval, 1.08-3.12; P = 0.03). CONCLUSION: SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who underwent CR.

Arterial Stiffness Index and Exercise Tolerance in Patients Undergoing Cardiac Rehabilitation.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (ß = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients.

BACKGROUND: Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. METHODS: We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). RESULTS: The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <  0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <  0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). CONCLUSION: High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.

Impact of Physical Activity on Coronary Plaque Volume and Components in Acute Coronary Syndrome Patients After Early Phase II Cardiac Rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA. CONCLUSIONS: No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Haemodynamic effects of acute intravenous landiolol in Takotsubo cardiomyopathy with dynamic left ventricular outflow tract obstruction.

Takotsubo cardiomyopathy (TCM) leads to serious left ventricular outflow tract (LVOT) obstruction with cardiogenic shock in 6%-20% of cases. The onset of LVOT obstruction, coupled with mitral regurgitation resulting from systolic anterior motion of mitral valve leaflets, can lead to haemodynamic instability in addition to severely impaired systolic function. We describe three patients who experienced chest discomfort following emotional stress. These patients displayed pronounced abnormalities on ECGs, insignificant obstructive coronary disease and haemodynamic instability due to LVOT obstruction. The infusion of landiolol, a short-acting beta blocker, was effective in releasing the gradient. Dynamic outflow obstruction is the major predictor of haemodynamic collapse. We suggested that an early identification of this complication in hypotensive patients with suspected TCM could be of utmost importance to optimise the therapeutic approach in the acute setting.

Three-dimensional optical coherence tomography to decide on reverse wire technique in bifurcation interventions.

A 79-year-old male with effort angina was admitted to receive optical coherence tomography (OCT)-guided percutaneous coronary intervention for restenosis of an everolimus-eluting stent implanted to the left anterior descending artery (LAD) eight years ago.

Safety and Feasibility of Tele-Cardiac Rehabilitation Using Remote Biological Signal Monitoring System: A Pilot Study.

Background: Cardiac rehabilitation (CR) is categorized as a class I recommendation in the guidelines for the management of patients with cardiovascular disease (CVD). However, the penetration rate of outpatient CR is low in Japan. We designed a pilot study to evaluate the safety and feasibility of tele-CR using a remote biological signal monitoring system. Methods: A total of nine patients (median aged 70.0 (66.0 - 76.0) years (male = 6) with CVD who participated in phase II CR for 1 month under the exercise prescription using the cardiopulmonary exercise test (CPET) were analyzed. They participated in the tele-CR program with a remote biological signal monitoring system (Nipro HeartLineTM, Osaka, Japan, and Duranta, Miyagi, Japan) in the CR room and were instructed by the CR staff from a separate room in the hospital. We evaluated the occurrence and degree of remote biological signal monitoring defects as safety evaluation items, i.e., whether the patients could set the remote biological signal monitoring equipment, as a feasibility evaluation item during a 3-month period. We also performed CPET at the baseline and follow-up. Following the 3-month tele-CR program, a total of 122 remote CR programs were performed using the remote biological signal monitoring system. Results: No patient experienced a lack of remote biological signal monitoring during exercise therapy. Significant improvement was noted in the exercise capacity, as assessed using the cardiopulmonary test (from 19.5 (16.7 - 20.2) mL/kg/min to 21.1 (17.3 - 22.8) mL/kg/min, P = 0.01, age ratio from 86% (75-96%) to 99% (78-104%), P = 0.01). One patient required support using the remote biological signal monitoring system, including information technology literacy. Conclusions: This study suggests the safety and feasibility of tele-CR using the remote biological signal monitoring system. However, further investigations are required to explore the suitability, effects, and cost-effectiveness of tele-CR as an alternative to center-based CR in the future.

Nutritional Status in Patients Undergoing Phase II Cardiac Rehabilitation by Mini Nutritional Assessment.

Background: Malnutrition impairs quality of life and prognosis of patients with cardiovascular disease. The Mini Nutritional Assessment (MNA) is a screening tool developed for the nutritional assessment of older adults. However, usefulness of MNA for patients undergoing cardiac rehabilitation (CR) has not been fully investigated. Methods: From March 2017 to September 2019, the MNA-short form (MNA-SF) and the MNA total score in patients undergoing phase II CR at the Juntendo University Hospital were evaluated. Results: A total of 336 patients (mean age 70.1 ± 11.4 years; males: 209) were analyzed. In the MNA-SF, 157 patients (47%) were found to be malnourished or at risk of malnutrition. In MNA total score, 168 patients (50%) were found to be malnourished or at risk of malnutrition. The MNA-SF < 12 group had significantly lower body mass index (BMI), hemoglobin level, low MNA scores for protein/water intake, self-evaluation of nutrition and health, and upper arm and calf circumferences compared to the MNA-SF ≥ 12 group. Assuming BMI < 18.5 as malnutrition, the sensitivity and specificity for malnutrition were 100% and 58.9% for MNA-SF, and 96.9% and 54.9% for MNA total score, respectively. Conclusions: MNA is useful in screening for malnutrition in patients undergoing CR. Approximately 50% of them were determined to be malnourished or at risk of malnutrition, suggesting the need for detailed evaluation regarding their food intake and dietary intervention.

Effects of Phase II Cardiac Rehabilitation on Physical Function and Anxiety Levels in Frail Patients.

Background: Frailty is an important prognostic factor in patients with cardiovascular diseases (CVD), and patients with CVD have a high rate of concurrent psycho-emotional stress, as well as depressive mood and anxiety symptoms. Despite this, few reports have examined the effects of the efficacy of Phase II cardiac rehabilitation (CR) in frail patients, including improvements in anxiety levels. Methods and Results: In all, 137 patients (mean [±SD] age 65.8±13.0 years; 71% male) who participated in Phase II CR and were assessed after CR completion were included in this study. Patients were evaluated using the Kihon Checklist (KCL) form at the beginning of CR and were divided into the 3 groups according to KCL scores: frail (n=34, 25%), pre-frail (n=40, 29%), and non-frail (n=63, 46%). Physical function and anxiety levels were compared among the 3 groups. The pre-frail and frail groups had significantly higher state anxiety and trait anxiety than the non-frail group (P<0.01). At the end of Phase II CR, all 3 groups showed significant improvements in the 6-min walking distance (P<0.05). State anxiety improved significantly in the non-frail and pre-frail groups, whereas trait anxiety only improved in the non-frail group. Conclusions: Physical function was improved in frail patients who participated in Phase II CR. However, there was no significant improvement in their level of anxiety.

Association Between Constipation and Frailty Components in Patients Undergoing Late Phase II Cardiac Rehabilitation.

BACKGROUND: The Japanese Ministry of Health, Labour and Welfare reported that the overall constipation complaint rates among men and women are 2.5% and 4.6%, respectively. To evaluate the impact of constipation on patients with cardiovascular diseases, we investigated the association between constipation and frailty components in patients undergoing cardiac rehabilitation (CR). METHODS: We enrolled 102 consecutive patients undergoing late phase II CR (mean age: 62.7 ± 13.4 years; 68 (67%) were men). We investigated clinical characteristics, observed defecation status and evaluated frailty components assessed by the Kihon checklist. According to the Clinical Guidelines for Chronic Constipation, the subjects were divided into constipation and non-constipation groups. RESULTS: Constipation was noted in 33 patients (32%). Interestingly, the constipation complaint rate was only 15%. Age was significantly higher in the constipation group than in the non-constipation group; however, no differences in sex, underlying diseases and prevalence rates of coronary risk factors were observed between the two groups. Body mass index, hemoglobin level, albumin level and estimated glomerular filtration rate were significantly lower in the constipation group than in the non-constipation group. The prevalence of frailty was significantly higher in the constipation group than in the non-constipation group. Physical ability, seclusion and depression scores were significantly higher in the constipation group than the non-constipation group. CONCLUSIONS: Constipation was associated with physical function and depression score as components of frailty in patients undergoing CR.

Prognostic impact of peak oxygen uptake and heart rate reserve in patients after off-pump coronary artery bypass grafting.

BACKGROUND: Peak oxygen uptake (peak VO2 ) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO2 and HRR on long-term prognosis after off-pump coronary artery bypass grafting (OP-CABG) remains unclear. HYPOTHESIS: To determine the prognostic impact of peak VO2 and HRR in patients after OP-CABG. RESULTS: We enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP-CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow-up period of 103 months. The non-survivor had significantly lower levels of peak VO2 (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p < .01) and HRR (24.2 ± 1.8 vs. 32.7 ± 0.8 beats/min, p < .01) than the survivor. In both groups, peak VO2 significantly correlated with HRR (p < .01). Moreover, patients were divided into four groups according to the peak VO2 and HRR levels for predicting total mortality. The low-peak VO2 /low-HRR group had a significantly higher mortality risk than the other groups (hazards ratio, 5.61; 95% confidence interval, 2.59-12.16; p < .01). After adjusted the confounding factors, peak VO2 and HRR were independently associated with total mortality (both p < .05). CONCLUSIONS: HRR is a simple parameter of CPET and an important prognostic marker for the risk stratification of total mortality even in patients with low-peak VO2 after OP-CABG.

Preliminary Pilot Study of Combined Effects of Physical Activity and Achievement of LDL-Cholesterol Target on Coronary Plaque Volume Changes in Patients with Acute Coronary Syndrome.

BACKGROUND: We investigated the combined effects of physical activity (PA) and aggressive low-density lipoprotein cholesterol (LDL-C) reduction on the changes in coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) using volumetric intravascular ultrasound (IVUS) analysis. METHODS: We retrospectively analyzed data from two different prospective clinical trials that involved 101 ACS patients who underwent percutaneous coronary intervention (PCI) and assessed the non-culprit sites of PCI lesions using IVUS at baseline and at the follow-up. After PCI, all the patients participated in early phase II comprehensive cardiac rehabilitation. Patients were divided into four groups based on whether the average daily step count, measured using a pedometer, was 7000 steps of more and whether the follow-up LDL-C level was <70 mg/dL. At the time of follow-up, we examined the correlation of changes in the PV with LDL-C and PA. RESULTS: The baseline characteristics of the four study groups were comparable. At the follow-up, plaque regression in both the achievement group (PA and LDL-C reduction) was higher than that in the other three groups. In addition, plaque reduction independently correlated with increased PA and reduction in LDL-C level. CONCLUSIONS: Combined therapy of intensive PA and achievement of LDL-C target retarded coronary PV in patients with ACS.

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.

Relationship Between Kihon Checklist Score and Anxiety Levels in Elderly Patients Undergoing Early Phase II Cardiac Rehabilitation.

BACKGROUND: The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR). METHODS: We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out self-assessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels. RESULTS: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01). CONCLUSIONS: Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR.

Associations among circulating levels of follistatin-like 1, clinical parameters, and cardiovascular events in patients undergoing elective percutaneous coronary intervention with drug-eluting stents.

OBJECTIVES: Follistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI). METHODS AND RESULTS: A consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P < 0.01). After excluding patients with creatinine clearance < 60 mL/min and hsCRP ≥ 0.2 mg/dL, the remaining 214 were followed for a median of 5.1 years. Twenty (9.3%) patients experienced MACCE. Receiver operating characteristics curve analysis estimated an FSTL1 cutoff of 41.1 ng/mL to predict MACCE occurrence. Kaplan-Meier analysis found a higher MACCE rate in patients with high (≥ 41.1 ng/mL) than with low (< 41.1 ng/mL) FSTL1 (P < 0.01). Multivariate Cox hazard analysis found that high FSTL1 was an independent predictor of MACCE (hazard ratio 4.54, 95% confidence interval: 1.45-20.07, P < 0.01). CONCLUSION: High plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP.

Relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation.

AIM: The Kihon Checklist is a useful screening tool for assessing frailty in older individuals. However, the clinical significance of the Kihon Checklist in cardiac rehabilitation patients remains unclear. The present study aimed to evaluate the relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation. METHODS: We enrolled 845 consecutive patients (584 men, mean age 71 years) who participated in cardiac rehabilitation at Juntendo University Hospital, Tokyo, Japan, between November 2015 and October 2017. The patients were divided into non-frailty (n = 287), pre-frailty (n = 270) and frailty (n = 288) groups according to their Kihon Checklist scores. Cardiopulmonary exercise testing was carried out in 302 patients. RESULTS: The frailty group was older and had a higher prevalence of history of heart failure than the non-frailty group, although left ventricular ejection fraction did not differ significantly between groups. Nutritional index, trunk and limb muscle mass, lean body weight, and grip strength were significantly lower in the frailty and pre-frailty groups than those in the non-frailty group. In the cardiopulmonary exercise test, a stepwise significant decrease in peak oxygen uptake was observed across the three groups (non-frailty 17.2 ± 3.6, pre-frailty 16.0 ± 3.4, frailty 14.4 ± 3.5 mL/kg/min, P < 0.01). Multivariate regression analyses showed that the Kihon Checklist score was significantly and independently associated with peak oxygen uptake (r = -0.34, P < 0.0001). CONCLUSIONS: The Kihon Checklist, which was associated with frailty and exercise tolerance, could be used as a clinical assessment method for patients who participated in cardiac rehabilitation. Geriatr Gerontol Int 2019; 19: 287-292.

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.