Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Comparison of intradialytic continuous and interval training on hemodynamics and dialysis adequacy: A crossover randomized controlled trial.

AIM: Circulating blood volume (BV) during exercise changes depending on the intensity and duration, and post-exercise hypotension is observed after continuous exercise. We investigated the safety and efficacy of both interval and continuous IDE at anaerobic threshold (AT) levels with respect to hemodynamic stability and dialysis efficiency. METHODS: In this crossover randomized controlled trial, 16 patients on haemodialysis were subjected to three trial arms, including non-IDE, interval-IDE, and continuous-IDE arms. Systolic blood pressure (SBP), BV, and ultraviolet absorbance - an indicator of dialysis efficiency - were continuously measured, and each change was compared between the three arms by two-way analysis of variance. RESULTS: Continuous IDE decreased SBP from post-exercise to the end of dialysis compared with baseline (pre 142.8 ± 19.0 vs. post 127.5 ± 24.5 mmHg, p = .02), whereas interval IDE maintained better SBP levels post-exercise (pre 139.9 ± 17.1 vs. post 140.1 ± 15.8 mmHg, p = 1.0) than continuous IDE (non-IDE 133.2 ± 19.9 vs. interval 140.1 ± 15.8 vs. continuous 127.5 ± 24.5 mmHg, p = .04). Moreover, interval IDE caused less tiredness and few symptoms (p < .05), despite reaching higher intensity than continuous IDE (p = .001). The BV of each IDE arm decreased during exercise and recovered post-exercise to the same level as non-IDE. Ultraviolet absorbance was not different between each arm (p = .16). CONCLUSION: AT-level interval IDE maintains better hemodynamic stability from post-exercise to the end of dialysis and may represent a novel approach that can be effectively performed with fewer symptoms.

Association of Postexercise Vagal Dysfunction With Protein-Energy Wasting and Noncardiovascular Outcomes in Patients Receiving Hemodialysis: A Retrospective Cohort Study.

OBJECTIVE: Postexercise vagal dysfunction is linked to noncardiovascular mortality in hemodialysis patients, but the mechanism is unknown. This study aimed to determine the association of cardiovagal neuropathy with systemic inflammation, protein-energy wasting, and noncardiovascular hospitalization. METHODS: This 2-center retrospective cohort study analyzed data from 280 hemodialysis patients who underwent exercise test. Patients were assessed for heart rate (HR) recovery (bpm) for 1 minute after exercise, a marker of vagal function, and were divided into 3 categories (Low: ≤ 6, Mid: 7-11, High: ≥ 12 bpm). We followed 1-year changes in the systemic inflammation-based prognostic score (Glasgow Prognostic Score [GPS]), body weight, and creatinine generation rate (CGR), an indicator of muscle mass, as well as 2-year hospitalization. RESULTS: The HR recovery category was associated with serum C-reactive protein and albumin levels and GPS. After 1 year, the low HR recovery category was associated with worsening in GPS (low, 0 [0-0.5]; mid, 0 [0-1]; high, 0 [0-0]), weight (low, 100.0 [96.1-102.5]; mid, 101.3 [98.9-105.0]; high, 100.5 [98.2-102.9]%), and CGR (low, 97.0 [88.5-111.4]; mid, 110.2 [90.9-124.8]; high, 106.2 [95.5-115.5]%), and the correlations with GPS and CGR remained consistent after adjusting for confounders such as exercise capacity and hospitalization during the follow-up period. There were 117 patients hospitalized. Compared to the high HR recovery category, the mid (hazard ratio: 1.8, 95% confidence interval [CI]: 1.1-3.1, P = .02) and low (hazard ratio: 2.4, 95% CI: 1.5-4.0, P = .001) categories were independently associated with an increased risk of all-cause hospitalization. For noncardiovascular disease hospitalization, the low HR recovery category was independently associated with increased risk of hospitalization (hazard ratio: 2.1, 95% CI: 1.2-3.7, P = .007). CONCLUSIONS: Vagal neuropathy in this population can contribute to adverse outcomes associated with systemic inflammation and protein-energy wasting.

Relationships between frailty and exercise capacity in patients undergoing hemodialysis: A cross-sectional study.

AIM: Hemodialysis (HD) patients have a high prevalence of frailty. The association between frailty and exercise capacity in HD patients has not been established. This study aimed to clarify the relationships between frailty and exercise capacity in HD patients. METHODS: This two-center cross-sectional study included HD patients who performed cardiopulmonary exercise testing. Participants were divided by frailty phenotype into robust, pre-frail, and frail using the revised Japanese version of the Cardiovascular Health Study criteria. Peak oxygen uptake (peakVO2 ) measured by cardiopulmonary exercise testing was compared with each frailty phenotype. The association between peakVO2 and frailty phenotype was analyzed using multivariate linear regression analysis adjusted for age, sex, body mass index diabetes mellitus, cardiovascular disease, cancer, history of fracture, hemoglobin, left ventricle ejection fraction, and percentage of heart rate reserve. RESULTS: The study included 136 patients (median age, 71.0 years; female, 23.5%), with 15.4%, 44.9%, and 39.7% with frailty phenotypes robust, pre-frail, and frail, respectively. PeakVO2 decreased with deterioration of the frailty phenotype (robust, median 15.1 [13.7-18.3] mL/min/kg; pre-frail, median 12.2 [10.5-14.4] mL/min/kg; frail, median 10.6 [9.2-12.5] mL/min/kg, P < 0.05). PeakVO2 decline was significantly associated with frail (B = -2.19, P = 0.004). Modeling individual frailty components showed a significant association between peakVO2 , usual gait speed (B = 2.38, P = 0.04), and low physical activity (B = -1.44, P = 0.004). CONCLUSION: Frailty in HD patients was associated with a decline in exercise capacity. HD patients with frailty need to improve exercise capacity, gait speed, and physical activity. Geriatr Gerontol Int 2023; 23: 795-802.

An equation to predict peak heart rate for prescribing exercise intensity in middle-aged to older patients requiring hemodialysis.

PURPOSE: Exercise prescription based on a population-specific physiological response can help ensure safe and effective physical interventions. However, as a facile approach for exercise prescription in hemodialysis population that is based on their exercise capacity has not yet been established, the aim of our study was to develop a unique prediction formula for peak heart rate (HR) that can be used in this population. METHODS: This cross-sectional study measured physical function and HR at peak exercise and anaerobic threshold (AT) during cardiopulmonary exercise tests in 126 individuals. Participants were randomly assigned to the development group (n = 78), whose data were used to calculate the prediction equation, or the validation group (n = 48). RESULTS: The HR reserve in this population was significantly lower (0.44 ± 0.20%) and there was a large discrepancy between conventional age-predicted maximal HR and measured peak-HR values (R = 0.36). The average of the ratio between HR at AT point and peak HR was 85% (95% CI, 83.5%-86.4%). The peak-HR prediction equation was based on resting HR, presence of diabetes, physical dysfunction (gait speed < 1.0 m/s), and hypoalbuminemia (< 3.5 g/dL). It showed high prediction accuracy (R2 [95%CI] = 0.71 [0.70-0.71]) with similar correlation coefficients between the development and validation groups (R = 0.82). CONCLUSION: Aerobic exercise based on estimated peak HR < 85% obtained from the equation in this study may enable safe and effective physical intervention in this population.

Association of cardiac autonomic neuropathy assessed by heart rate response during exercise with intradialytic hypotension and mortality in hemodialysis patients.

The heart rate (HR) reflects the dynamic behavior of the autonomic nervous system, and HR profiles during the exercise test provide prognostic information. However, there are no reports of these factors in hemodialysis patients. Data from 256 patients (mean 68.8 years old) who underwent an exercise test were statistically analyzed. Patients were evaluated for the percent HR reserve from HR at peak exercise, HR recovery for one minute after peak exercise, and exercise capacity, as well as intradialytic hypotension (IDH). The prevalence of chronotropic incompetence (96.1%), defined as under 80% HR reserve, and abnormal HR recovery (60.5%), defined as under 12 beats, were very common. Eighty-four deaths occurred during the follow-up period (median, 3.8 years). A slow HR recovery under 7 beats was associated with IDH after adjustment (odds ratio 2.7, 95% confidence interval 1.1-6.4). HR recovery under 12 beats (hazard ratio over study period 5.1, 95% confidence interval 2.5-10.5), HR reserve under 26.2% (3.4, 1.7-6.8), and IDH (1.7, 1.1-2.8) were associated with all-cause mortality after adjustment. Considering the confounding of all three variables, only HR recovery under 12 beats remained associated with the all-cause and cause-specific mortality ("cardiovascular" and "non-cardiovascular"). This association was consistent even in subgroup analyses based on the presence of diabetes and cardiovascular disease. Thus, HR profiles during the exercise can reflect potential health conditions related to cardiac autonomic neuropathy in hemodialysis patients that affect IDH and their survival.

Effect of blood volume change related to intensity of intradialytic aerobic exercise on hemodialysis adequacy: a pilot study.

PURPOSE: Intradialytic exercise may improve dialysis efficiency; however, the association between changes in blood volume (BV) related to exercise intensity and solute removal kinetics remains unknown. We herein investigated the relationship between changes in BV with exercise and removal of solute molecules during hemodialysis. METHODS: Each of the 21 hemodialysis patients underwent cardiopulmonary exercise test to measure anaerobic threshold (AT). According to the exercise intensity, patients were classified into two groups, the low group (n = 12), whose intensity was below the AT, and the high group (n = 9), whose intensity was at the AT level. Each patient completed two trial arms of resting and discontinuous exercise dialysis sessions in a randomized manner. RESULTS: The change in BV with the exercise dialysis session in the high group decreased during exercise (p = 0.028) and remained decreased after exercise (p = 0.016), compared with the low group. In the low group, compared with routine sessions, the removal of potassium (p = 0.030), phosphate (p = 0.024), and urea nitrogen (p = 0.065) increased during exercise, but the total removal of these solutes did not change. In the high group, the removal of phosphate (p < 0.001) and urea nitrogen (p = 0.018) after exercise and even total phosphate (p = 0.027) decreased. CONCLUSION: These findings suggest that the removal of small solute molecules is improved during exercise in intradialytic low-intensity exercise with no change in BV, and decreased after exercise in high-intensity exercise with a decrease in BV. CLINICAL TRIALS REGISTRY: Trial retrospectively registered at the UMIN Clinical Trials Registry: study number UMIN000038629 (Registration date: September 7, 2019).

Association between social frailty as well as early physical dysfunction and exercise intolerance among older patients receiving hemodialysis.

BACKGROUND: Recently, social frailty has been increasingly recognized as a factor associated with adverse health outcomes, including physical disability and mortality. However, there are no studies about the importance of this factor among hemodialysis patients. Therefore, we investigated the relationship between social frailty and early physical dysfunction in this group of patients. METHODS: This was a two-center cross-sectional study. Older patients receiving hemodialysis were prospectively enrolled. Moreover, participants were evaluated for social frailty based on the definition of previous study and for physical function, peak oxygen uptake (peak VO2 ), ventilatory equivalent for carbon dioxide (VE/VCO2 ) slope and heart rate reserve. Then, they were divided into two groups based on the presence of physical frailty. RESULTS: Data collected from 158 individuals were statistically analyzed. The prevalence rate of social frailty was 59.5%. In the non-physical frailty group, social frailty was found to be independently associated with reduced gait speed (P = 0.007), leg strength (P = 0.040) and peak VO2 (P = 0.023), but not with hand grip strength (P = 0.36). In the physical frailty group, there was no association between social frailty and physical function. Moreover, in patients without physical and social frailty, physical function was maintained at above accepted threshold levels, whereas peak VO2 (14.1 ± 3.3 mL/kg/min), VE/VCO2 slope (32.3 ± 5.5) and heart rate reserve (50.8% ± 21.7%) were substantially impaired. CONCLUSIONS: Patients receiving hemodialysis can present with social frailty and exercise intolerance with cardiac dysfunction in the early phase, which may contribute to subsequent dysfunction. Geriatr Gerontol Int 2021; 21: 664-669.

Acute Effect of Whole-Body Periodic Acceleration on Brachial Flow-Mediated Vasodilatation Assessed by a Novel Semi-Automatic Vessel Chasing UNEXEF18G System.

BACKGROUND: Repeated application of whole-body periodic acceleration (WBPA) upregulates endothelial nitric oxide synthase and improves brachial artery endothelial function (BAEF) as assessed by measurement of flow-mediated vasodilatation (FMD). However, the acute effect of a single application of WBPA on BAEF has not been fully characterized. In addition, although a novel semi-automatic vessel chasing system (UNEXEF18G) has now been developed in Japan, the direct comparison of UNEXEF18G with a conventional method for FMD measures has not been conducted even if UNEXEF18G has already been utilized in a relatively large scale study. METHODS: We have developed a novel semi-automatic vessel chasing system (UNEXEF18G) that can measure FMD on-line, identify time to peak vasodilatation (TPV), and determine the area under the vasodilatation curve (AUC). Thus, 45 min of WBPA was applied in 20 healthy volunteers (age, 34 ± 13 years), and BAEF was measured by UNEXEF18G before and after WBPA. Also, UNEXEF18G measured FMD was compared with those of a conventional FMD measurement method at rest in order to validate a novel UNEXEF18G measured FMD. RESULTS: Single WBPA resulted in a significant increase in FMD (from 6.4 ± 3.4 to 10.7 ± 4.3%, p < 0.01), a significant decrease in TPV and a significant increase in AUC. In the validation study for UNEXEF18G, Bland and Altman analysis showed that UNEXEF18G measured FMD was almost identical to those of the conventional method at rest. CONCLUSION: These data suggest the usefulness of a new UNEXEF18G and that single application of WBPA results in acute improvement in BAEF in humans.

Newly developed mobile mass superimposed on mitral annulus calcification in patient with cerebral infarction: Documentation of a unique embolic source.

Mitral annulus calcification (MAC) has been recognized as a potent risk factor to cause cerebral infarction. There has been suggested possible linkage between mass on MAC and systemic embolic events. We report a case of cerebral infarction with newly developed mobile mass superimposed on MAC.

Mobile and accurate detection system for infection by the 2009 pandemic influenza A (H1N1) virus with a pocket-warmer reverse-transcriptase loop-mediated isothermal amplification.

The 2009 pandemic H1N1 influenza A virus spread quickly worldwide in 2009. Since most of the fatal cases were reported in developing countries, rapid and accurate diagnosis methods that are usable in poorly equipped laboratories are necessary. In this study, a mobile detection system for the 2009 H1N1 influenza A virus was developed using a reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) kit with a disposable pocket-warmer as a heating device (designated as pwRT-LAMP). The pwRT-LAMP can detect as few as 100 copies of the virus--which is nearly as sensitive as real-time reverse-transcription polymerase chain reaction (RT-PCR)--and does not cross-react with RNA of seasonal influenza viruses. To evaluate the usefulness of the pwRT-LAMP system, nasal swab samples were collected from 56 patients with flu-like symptoms and were tested. Real-time RT-PCR confirmed that the 2009 H1N1 influenza A virus was present in 27 of the 56 samples. Of these 27 positive samples, QuickVue Influenza A+B immunochromatography detected the virus in only 11 samples (11/27; 40.7%), whereas the pwRT-LAMP system detected the virus in 26 of the 56 samples (26/27 of the positive samples; 96.3%). These findings indicate that the mobile pwRT-LAMP system is an accurate diagnostic system for the 2009 H1N1 influenza A virus, and has great potential utility in diagnosing future influenza pandemics.

Endothelial Function as a Possible Significant Determinant of Cardiac Function during Exercise in Patients with Structural Heart Disease.

This study was investigated the role that endothelial function and systemic vascular resistance (SVR) play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST) in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT) was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD) was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis.

BACKGROUND: While both flow-mediated vasodilation (FMD) in the brachial artery (BA), which measures endothelium-dependent vasodilatation, and intima-media thickness (IMT) in the carotid artery are correlated with the prognosis of coronary artery disease (CAD), it is not clear which modality is a better predictor of CAD. Furthermore, it has not been fully determined whether either of these modalities is superior to conventional ST-segment depression on exercise stress electrocardiogram (ECG) as a predictor. Thus, the goal of the present study was to compare the predictive value of FMD, IMT, and stress ECG for CAD prognosis. METHODS AND RESULTS: A total of 103 consecutive patients (62 +/- 9 years old, 79 men) with clinically suspected CAD had FMD and nitroglycerin-induced dilation (NTG-D) in the BA, carotid artery IMT measurement using high-resolution ultrasound, and exercise treadmill testing. The 73 CAD patients and 30 normal coronary patients were followed for 50 +/- 15 months. Fifteen patients had coronary events during this period (1 cardiac death, 2 non-fatal myocardial infarctions, 3 acute heart failures, and 9 unstable anginas). On Kaplan-Meier analysis, only FMD and stress ECG were significant predictors for cardiac events. CONCLUSION: Brachial endothelial function as reflected by FMD and conventional exercise stress testing has comparable prognostic value, whereas carotid artery plaque burden appears to be less powerful for predicting future cardiac events.

Comparative predictive and diagnostic value of flow-mediated vasodilation in the brachial artery and intima media thickness of the carotid artery for assessment of coronary artery disease severity.

BACKGROUND: While recent reports suggest that both flow-mediated vasodilation (FMD) in the brachial artery (BA), endothelium-dependent vasodilatation, and intima media thickness (IMT) in the carotid artery correlate with the extent of coronary artery disease (CAD), it is not clear which modality is a better predictor for CAD severity and whether either of these modalities are superior to conventional ST-segment depression in exercise stress electrocardiogram (ECG). Thus, the goal of the present study was to compare the predictive value of FMD and IMT for CAD severity and to evaluate the diagnostic accuracy. STUDY: A total of 103 consecutive patients (62+/-9 years, 79 men) with clinically suspected CAD underwent FMD and nitroglycerin-induced dilation (NTG-D) in the BA as well as measurement of carotid artery IMT by using high-resolution ultrasound, and exercise treadmill testing. Coronary stenosis index (CSI) was calculated from coronary angiography. RESULTS: Seventy-three patients had significant CAD, and 30 patients showed no CAD (NL). FMD was significantly lower and IMT was significantly higher in patients with CAD compared with NL patients (FMD, 3.7+/-3.0% vs. 7.5+/-2.9%; IMT, 1.1+/-0.2 mm vs. 0.7+/-0.1 mm). FMD and IMT correlated to CSI to a similar degree (r=-0.67, r=0.69, respectively), and there was a significant correlation between FMD and IMT. In contrast, NTG-D did not correlate with CSI or IMT. Further, the diagnostic accuracy of FMD and IMT was comparable or even better than that obtained with conventional ST-segment depression during exercise in this cohort. CONCLUSIONS: FMD in BA and IMT could represent a surrogate diagnostic method for assessment of CAD severity.

Association of takotsubo cardiomyopathy and long QT syndrome.

A young woman presented with takotsubo cardiomyopathy after a syncopal attack caused by torsades de pointes. Two-dimensional echocardiography on admission showed left ventricular apical akinesis (ballooning) and basal hyperkinesis, compatible with takotsubo cardiomyopathy. This gradually normalized in 2 months. ECG on admission showed remarkable QT prolongation, U waves, and negative T waves, which also gradually normalized. Coronary angiography revealed no organic stenosis; however, acetylcholine provocation test caused the QT interval to again become prolonged. During treadmill exercise stress testing, the QT interval shortened as heart rate increased. Therefore, without genetic analysis, this patient was considered to have sporadic long QT syndrome in which takotsubo cardiomyopathy developed after the syncopal attack caused by torsades de pointes.

Beneficial effects of nifedipine on vasodilator response to acetylcholine in coronary and brachial arteries in the patients with coronary artery disease.

BACKGROUND: Nifedipine has been reported to improve endothelial function. However, there are few simultaneous studies on the effects of nifedipine on coronary and peripheral endothelial function in humans. METHODS: To investigate the effects of nifedipine on endothelial function in coronary artery (CA) and brachial artery (BA) in coronary artery disease (CAD), we measured vasodilator responses of CA and BA to acetylcholine (ACh, endothelium-dependent dilation) in 13 patients (63+/-10 years old) with CAD before and after sublingual administration of nifedipine 10 mg. To measure blood flow, a Doppler guidewire was inserted into the major branch of CA and the left BA. ACh was infused at 10(-7) mol/l for 3 min into CA and at 15.0 microg/ml for 5 min into BA, respectively. The vasodilator response to ACh was assessed by the ratio of ACh-induced flow/baseline flow (CAVR index, the ratio of CA flow changed by ACh; BAVR index, the ratio of BA flow changed by ACh). RESULTS: Nifedipine significantly increased both the CAVR and BAVR index:CAVR index, from 1.33+/-0.54 to 1.76+/-0.52 (32%) and BAVR index, from 1.74+/-0.83 to 2.18+/-0.93 (25%), respectively, p<0.05. In addition, nifedipine-induced changes in CAVR tended to correlate with those of BAVR (r=0.42. p=0.06). CONCLUSIONS: Acute administration of nifedipine improves both coronary and brachial artery vasodilator responses to ACh. Nifedipine improves coronary and peripheral endothelial function in patients with CAD.