Cancer history and physical function in patients with cardiovascular disease.

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61-77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan-Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4-5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis.

Reactive metabolite of trovafloxacin activates inflammasomes: Implications for trovafloxacin-induced liver injury.

Trovafloxacin is a quinolone antibiotic drug with broad-spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury. The characteristics of trovafloxacin-induced liver injury are consistent with an idiosyncratic reaction; however, the details of the mechanism have not been elucidated. We examined whether trovafloxacin induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes. We also tested ciprofloxacin, levofloxacin, gatifloxacin, and grepafloxacin for their ability to activate inflammasomes. Drug bioactivation was performed with human hepatocarcinoma functional liver cell-4 (FLC-4) cells, and THP-1 cells (human monocyte cell line) were used for the detection of inflammasome activation. The supernatant from the incubation of trovafloxacin with FLC-4 cells for 7 days increased caspase-1 activity and production of IL-1ß by THP-1 cells. In the supernatant of FLC-4 cells that had been incubated with trovafloxacin, heat shock protein (HSP) 40 was significantly increased. Addition of a cytochrome P450 inhibitor to the FLC-4 cells prevented the release of HSP40 from the FLC-4 cells and inflammasome activation in THP-1 cells by the FLC-4 supernatant. These results suggest that reactive metabolites of trovafloxacin can cause the release of DAMPs from hepatocytes that can activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by trovafloxacin, which, in some patients, can cause immune-related liver injury.

Relationship between the spread of COVID-19, social frailty, and depressive symptoms in patients with heart failure.

In community-dwelling older people, coronavirus disease 2019 (COVID-19) has been reported to be associated with the development of frailty and depressive symptoms. We aimed to investigate whether the spread of COVID-19 is associated with the development of frailty in patients with heart failure (HF). The presence of the multi-domain of frailty in 257 patients with HF was assessed at hospital discharge. The spread of COVID-19 was significantly associated with the development of social frailty and depressive symptoms. Evaluation of these symptoms during hospitalization would support disease management and understanding of their social and psychological conditions.

Effects of Acute Phase Intensive Physical Activity (ACTIVE-PA) Monitoring and Education for Cardiac Patients: Pilot Study of a Randomized Controlled Trial.

BACKGROUND: Although physical activity (PA) decreases dramatically during hospitalization, an effective intervention method has not yet been established for this issue. We recently developed a multiperson PA monitoring system using information and communication technology (ICT) that can provide appropriate management and feedback about PA at the bedside or during rehabilitation. This ICT-based PA monitoring system can store accelerometer data on a tablet device within a few seconds and automatically display a graphical representation of activity trends during hospitalization. OBJECTIVE: This randomized pilot study aims to estimate the feasibility and effect size of an educational PA intervention using our ICT monitoring system for in-hospital patients undergoing cardiac rehabilitation. METHODS: A total of 41 patients (median age 70 years; 24 men) undergoing inpatient cardiac rehabilitation were randomly assigned to 2 groups as follows: wearing an accelerometer only (control) and using both an accelerometer and an ICT-based PA monitoring system. Patients assigned to the ICT group were instructed to gradually increase their step counts according to their conditions. Adherence to wearing the accelerometer was defined as having enough wear records for at least 2 days to allow for adequate analysis during the lending period. An analysis of covariance was performed to compare the change in average step count during hospitalization as a primary outcome and the 6-minute walking distance at discharge. RESULTS: The median duration of wearing the accelerometer was 4 days in the ICT group and 6 days in the control group. Adherence was 100% (n=22) in the ICT group but 83% (n=20) in the control group. The ICT group was more active (mean difference=1370 steps, 95% CI 437-2303) and had longer 6-minute walking distances (mean difference=81.6 m, 95% CI 18.1-145.2) than the control group. CONCLUSIONS: Through this study, the possibility of introducing a multiperson PA monitoring system in a hospital and promoting PA during hospitalization was demonstrated. These findings support the rationale and feasibility of a future clinical trial to test the efficacy of this educational intervention in improving the PA and physical function of in-hospital patients. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000043312; http://tinyurl.com/m2bw8vkz.

Trends and Outcomes of Early Rehabilitation in the Intensive Care Unit for Patients With Cardiovascular Disease: A Cohort Study With Propensity Score-Matched Analysis.

BACKGROUND: The effectiveness of acute-phase cardiovascular rehabilitation (CR) in intensive care settings remains unclear in patients with cardiovascular disease (CVD). This study aimed to investigate the trends and outcomes of acute-phase CR in the intensive care unit (ICU) for patients with CVD, including in-hospital and long-term clinical outcomes. METHOD: This retrospective cohort study reviewed a total of 1,948 consecutive patients who were admitted to a tertiary academic ICU for CVD treatment and underwent CR during hospitalisation. The endpoints of this study were the following: in-hospital outcomes: probabilities of walking independence and returning home; and long-term outcomes: clinical events 5 years following hospital discharge, including all-cause readmission or cardiovascular events. It evaluated the associations of CR implementation during ICU treatment (ICU-CR) with in-hospital and long-term outcomes using propensity score-matched analysis. RESULTS: Among the participants, 1,092 received ICU-CR, the rate of which tended to increase with year trend (p for trend <0.001). After propensity score matching, 758 patients were included for analysis (pairs of n=379 ICU-CR and non-ICU-CR). ICU-CR was significantly associated with higher probabilities of walking independence (rate ratio, 2.04; 95% CI 1.77-2.36) and returning home (rate ratio, 1.22; 95% CI 1.05-1.41). These associations were consistently observed in subgroups aged >65 years, after surgery, emergency, and prolonged ICU stay. ICU-CR showed significantly lower incidences of all-cause (HR 0.71; 95% CI 0.56-0.89) and cardiovascular events (HR 0.69; 95% CI 0.50-0.95) than non-ICU-CR. CONCLUSIONS: The implementation of acute-phase CR in ICU increased with year trend, and is considered beneficial to improving in-hospital and long-term outcomes in patients with CVD and various subgroups.

Decreased plasma acetaminophen glucuronide/acetaminophen concentration ratio warns the onset of acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury (AILI) is the most common cause of acute liver failure. Although the mechanisms that trigger AILI are well known, it is less understood how to halt AILI progression and facilitate liver recovery. Therefore, it is necessary to understand the pathophysiology of APAP hepatotoxicity in patients and to examine predictive/preventive markers. In a clinical study, we had a case in which aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased in a patient with a low ratio of APAP glucuronide concentration (AP-G)/APAP plasma concentration. Then a reverse translational study was conducted for clarifying this clinical question. The relationship between plasma AP-G/APAP concentration ratio and the levels of AST and ALT was examined by in vivo and in vitro experiments. In in vivo experiments, 10-week-old rats showed lower UGT activity, lower AP-G/APAP concentration ratios, and higher AST and ALT levels than 5-week-old rats. This suggests an inverse correlation between the AP-G/APAP concentration ratio and the AST, ALT levels in APAP-treated rats. Furthermore, as a result of the in vitro experiment, it was confirmed that the cell viability decreased when the AP-G/APAP concentration ratio in the culture medium decreased. Since the decrease in the plasma AP-G/APAP concentration ratio appears earlier than the increase of AST and ALT levels, the ratio might be a presymptomatic marker of AILI. When APAP is used for a long time, it is recommended to perform therapeutic drug monitoring of the AP-G/APAP concentration ratio, which is a predictive/preventive marker of AILI.

Clinical Impact of Improvement in Sarcopenia through Cardiac Rehabilitation in Patients with Heart Failure.

OBJECTIVES: Sarcopenia in patients with heart failure (HF) is associated with poor prognosis. Cardiac rehabilitation (CR) decreases the incidence of adverse events in patients with HF. However, the clinical implications of improving sarcopenia status through CR remain unclear. This study investigated the relationship between the changes in sarcopenia status in patients with HF undergoing outpatient CR and the risk of mortality and adverse events. DESIGN: This was a retrospective cohort study of patients hospitalized at the Kitasato University Hospital Cardiovascular Center for the treatment of HF between January 2007 and December 2020. SETTING AND PARTICIPANTS: Patients with HF whose sarcopenia status was assessed at hospital discharge and following at least 3 months of outpatient CR were included. Based on the sarcopenia status, all patients were divided into 3 groups: patients without sarcopenia at discharge (ie, robust), patients with sarcopenia at discharge but no sarcopenia following CR (ie, improved), and patients with sarcopenia at discharge and following CR (ie, unimproved). METHODS: Cox regression analysis was used to examine the risk of all-cause death associated with the 3 sarcopenia status groups. RESULTS: Of 546 patients with HF (median age: 70 years; male: 63.6%), 377 (69.0%), 54 (9.9%), and 115 (21.1%) were classified as robust, improved, and unimproved, respectively. Multivariate Cox regression analysis showed that the unimproved group had a significantly greater risk of all-cause death when compared to the robust group [hazard ratio (HR) 2.603, 95% CI 1.375-4.930, P = .004], but it did not differ from the improved group (HR 1.403, 95% CI 0.598-3.293, P = .43). CONCLUSIONS AND IMPLICATIONS: No improvement in sarcopenia status in patients with HF undergoing outpatient CR was associated with a higher risk of all-cause death. Sarcopenia may be an important target to improve the prognosis of patients with HF.

Trajectory of Abdominal Skeletal Muscle Changes During Cardiac Rehabilitation in Patients With Aortic Disease.

OBJECTIVE: This study focused on routine computed tomography imaging for aortic disease management and evaluated the trajectory of skeletal muscle changes through inpatient and outpatient cardiac rehabilitation. DESIGN: Prospective observational study included patients who underwent abdominal computed tomography three times (baseline, postacute care, and follow-up). The area and density of the all-abdominal and erector spine muscles and intramuscular adipose tissue were measured. A generalized linear model with patients as random effects was used to investigate skeletal muscle changes. RESULTS: Thirty-nine patients completed outpatient cardiac rehabilitation, and 60 were incomplete. Skeletal muscle area significantly decreased from baseline to the follow-up period only in the incomplete rehabilitation group. Skeletal muscle density significantly decreased from baseline to postacute care and increased at the follow-up period, but only patients who completed rehabilitation showed recovery up to baseline at the follow-up period. These trajectories were more pronounced in the erector spine muscle. Intramuscular adipose tissue showed a trend of gradual increase, but only the incomplete rehabilitation group showed a significant difference from baseline to the follow-up period. CONCLUSIONS: The density of skeletal muscle may reflect the most common clinical course; skeletal muscle area and intramuscular adipose tissue are unlikely to improve positively, and their maintenance seemed optimal.

The Association between the Level of Ankle-Brachial Index and the Risk of Poor Physical Function in Patients with Cardiovascular Disease.

AIMS: The progression of atherosclerosis and decline in physical function are poor prognostic factors in patients with cardiovascular disease (CVD). The ankle-brachial index (ABI) is a widely used indicator of the degree of progression of atherosclerosis, which may be used to identify patients with CVD who are at risk of poor physical function. This study examined the association between ABI and poor physical function in patients with CVD. METHODS: We reviewed the data of patients with CVD who completed the ABI assessment and physical function tests (6-min walking distance, gait speed, quadriceps isometric strength, and short physical performance battery). Patients were divided into five categories according to the level of ABI, and the association between ABI and poor physical function was examined using multiple logistic regression analysis. Additionally, restricted cubic splines were used to examine the nonlinear association between ABI and physical function. RESULTS: A total of 2982 patients (median [interquartile range] age: 71[62-78] years, 65.8% males) were included in this study. Using an ABI range of 1.11-1.20 as a reference, logistic regression analysis showed that ABI ≤ 1.10 was associated with poor physical function. The restricted cubic spline analysis showed that all physical functions increased with an increase in ABI level. The increase in physical function plateaued at an ABI level of approximately 1.1. CONCLUSIONS: ABI may be used to identify patients with poor physical function. ABI levels below 1.1 are potentially associated with poor physical function in patients with CVD.

Screening for sarcopenia with SARC-F in older patients hospitalized with cardiovascular disease.

OBJECTIVES: SARC-F ≥ 4 points are used for detecting sarcopenia; however, finding a lower SARC-F cut-off value may lead to early detection of sarcopenia. We investigated the SARC-F score with the highest sensitivity and specificity value to identify sarcopenia in older patients with cardiovascular disease (CVD). Motor performances were also examined for each SARC-F score. METHODS: This retrospective cross-sectional study examined the sensitivity and specificity of every 1-point increase in SARC-F score to predict sarcopenia. Eligible participants included patients with CVD (≥ 65 years old) who were admitted for acute CVD treatment and participated in cardiac rehabilitation. Patients completed the SARC-F questionnaire and the sarcopenia assessment. Areas under the curves (AUCs) were investigated for the ability to predict sarcopenia. Multivariable linear regression was used to compare the mean value of physical functions (e.g., Walking speed, leg strength, and 6-minute walking distance) of each SARC-F score. RESULTS: A total of 1066 participants (63.8% male; median age: 78 years) were included. Sarcopenia was present in 401 patients. SARC-F cut-off ≥ 2 presented the optimal balance between sensitivity (68.3%) and specificity (55.6%) to detect sarcopenia (the AUCs = 0.658; 95% confidence interval: 0.625-0.691). Even when the patients have low scores (1-3), increasing every 1 point of SARC-F score was associated with lower physical functions, such as lower muscle strength and shorter walking distance (all p < 0.001). CONCLUSIONS: SARC-F cut-off ≥ 2 was optimal for screening sarcopenia, and even a low SARC-F score is helpful in finding earlier sarcopenia and low physical function in patients with CVD.

Association of sarcopenia defined by different skeletal muscle mass measurements with prognosis and quality of life in older patients with heart failure.

BACKGROUND: Diagnosing sarcopenia in heart failure (HF) patients is important, but how to assess skeletal muscle mass in HF patients with fluid retention is controversial. We aimed to examine the association between sarcopenia, defined by different skeletal muscle mass measurements, and clinical outcomes in older HF patients. METHODS: We included 546 older HF patients (≥ 65 years) who were assessed for sarcopenia at discharge (median age 77 years, 309 males). Sarcopenia was diagnosed using grip strength, usual gait speed, and skeletal muscle mass according to international criteria. We used mid-upper arm circumference (MUAC), mid-upper arm muscle circumference (MAMC), calf circumference (CC), and skeletal muscle mass index (SMI) assessed by bioelectrical impedance analysis to assess skeletal muscle mass and defined sarcopenia in each of these measurements. Prognostic outcomes were composite events (all-cause death and HF rehospitalization) and cardiovascular disease (CVD) events (CVD death and CVD rehospitalization). Quality of life (QOL) was assessed using the 36-item Short-Form Health Survey physical functioning (SF-36PF) score. RESULTS: The sarcopenia defined by MUAC [hazard ratio (HR): 2.50; 95 % confidence interval (95 % CI): 1.64-3.81; p < 0.001] or MAMC (HR: 1.98; 95 % CI: 1.35-2.92; p = 0.001) were associated with higher composite event rates than the non-sarcopenia. The sarcopenia defined by MUAC (HR: 1.88; 95 % CI: 1.25-2.83; p = 0.002) or MAMC (HR: 1.70; 95 % CI: 1.16-2.49; p = 0.007) were associated with higher CVD event rates than the non-sarcopenia. The sarcopenia defined by CC or SMI were not associated with prognoses. The sarcopenia defined by MUAC, MAMC, or CC were associated with low SF-36PF scores (all p < 0.05). CONCLUSIONS: These results suggest that a diagnosis of sarcopenia based on MUAC or MAMC rather than CC or SMI reflects prognosis and QOL in older HF patients.

Effect of change in hepato-renal function and cardiac rehabilitation on mortality in patients with heart failure.

BACKGROUND: Patients with heart failure (HF) often suffer from hepato-renal dysfunction. The associations between hepato-renal function changes and mortality remain unclear. Further, the effect of cardiac rehabilitation (CR) on mortality and motor functions in patients with HF and hepato-renal dysfunction requires investigation. METHODS: We reviewed 2522 patients with HF (63.2 % male; median age: 74 years). The association between changes in hepato-renal function assessed by the Model for End-stage Liver Disease eXcluding INR (MELD-XI) score and mortality was examined. The association of CR participation with mortality and physical functions was investigated in patients with HF with decreased, unchanged, and increased MELD-XI scores. RESULTS: During the follow-up period, 519 (20.6 %) patients died. Worsened MELD-XI score was independently associated with all-cause death [adjusted hazard ratio (aHR): 1.099; 95 % confidence interval (CI): 1.061-1.138; p < 0.001]. CR participation was associated with low mortality, even in the increased MELD-XI score group (aHR: 0.498; 95 % CI: 0.333-0.745; p < 0.001). Trajectory of the MELD-XI score was not associated with physical function changes. There were no time by MELD-XI score interaction effects on handgrip strength (p = 0.084), leg strength (p = 0.082), walking speed (p = 0.583), and 6-min walking distance (p = 0.833) in patients participating in outpatient CR. CONCLUSIONS: Hepato-renal dysfunction predicts high mortality. CR participation may be helpful for a better prognosis of patients with HF and hepato-renal dysfunction.

Leg strength and incidence of heart failure in patients with acute coronary syndrome.

AIMS: The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. It is unclear whether skeletal muscle strength, in addition to existing risk factors, is a predictor for developing HF after ACS. We aimed to clarify the relationship between quadriceps isometric strength (QIS), a skeletal muscle strength indicator, and the risk of developing HF in patients with ACS. METHODS AND RESULTS: We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization. The median (interquartile range) age was 67 (57-74) years. The patients were classified into two groups-high and low QIS-using the sex-specific median QIS. The endpoint was HF admissions. During a mean follow-up period of 4.4 ± 3.7 years, 75 (7.1%) HF admissions were observed. After multivariate adjustment, a high QIS was associated with a lower risk of HF [hazard ratio: 0.52, 95% confidence interval (CI): 0.32-0.87]. Hazard ratio (95% CI) per 5% body weight increment increase of QIS for HF incidents was 0.87 (0.80-0.95). Even when competing risks of death were taken into account, the results did not change. The inclusion of QIS was associated with increases in net reclassification improvement (0.26; 95% CI: 0.002-0.52) and an integrated discrimination index (0.01; 95% CI: 0.004-0.02) for HF. CONCLUSION: The present study showed that a higher level of QIS was strongly associated with a lower risk of developing HF after ACS. These findings suggest that skeletal muscle strength could be one of the factors contributing to the risk of developing HF after ACS.

The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. Basic attributes, coronary risk factors, and cardiac and renal function have been reported as risk factors for developing HF after ACS. However, the association between skeletal muscle strength and the development of HF after ACS is unclear. We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization and used quadriceps isometric strength (QIS) as a measure of skeletal muscle strength. We found that higher QIS was associated with a lower risk of developing HF after ACS. The results of our study suggest the benefit of assessing skeletal muscle strength in addition to basic attributes, coronary risk factors, and cardiac and renal function to assess the risk of developing HF after ACS.

Predictive value of the Ishii score for sarcopenia and the prognosis of older patients hospitalized with heart failure.

AIMS: Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure. METHODS: This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared. RESULTS: Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality. CONCLUSION: Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2024; 24: 147-153.

Unsaturated polyurethanes degradable by conjugate substitution reactions with amines and carboxylate anions.

Main-chain scission of polymers induces a significant decrease in molecular weight and accompanying changes in physical properties and is important for applications in materials engineering, such as in photoresists and adhesive dismantling. In this study, we focused on methacrylates substituted with carbamate groups at the allylic positions for the purpose of developing a mechanism that efficiently cleaves the main chain in response to chemical stimuli. Dimethacrylates substituted with hydroxy groups at the allylic positions were synthesized by the Morita-Baylis-Hillman reaction of diacrylates and aldehydes. The polyaddition with diisocyanates afforded a series of poly(conjugated ester-urethane)s. These polymers underwent a conjugate substitution reaction with diethylamine or acetate anion at 25 °C, resulting in main-chain scission accompanied by decarboxylation. A side reaction by the re-attack of the liberated amine end to the methacrylate skeleton proceeded, whereas it was suppressed for the polymers with an allylic substitute of the phenyl group. Therefore, the methacrylate skeleton substituted with phenyl and carbamate groups at the allylic position is an excellent decomposition point that induces selective and quantitative main-chain scission with weak nucleophiles, such as carboxylate anions.

Mechanism of non-steroidal anti-androgen-induced liver injury: Reactive metabolites of flutamide and bicalutamide activate inflammasomes.

Flutamide is a non-steroidal anti-androgen agent, which is mainly used for the treatment of prostate cancer. Flutamide is known to cause severe adverse events, which includes idiosyncratic liver injury. However, details of the mechanism of these adverse reactions have not been elucidated. We investigated whether flutamide induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes. We also tested bicalutamide, enzalutamide, apalutamide, and darolutamide for their ability to activate inflammasomes in differentiated THP-1 cells. The supernatant from the incubation of flutamide and bicalutamide with human hepatocarcinoma functional liver cell-4 (FLC-4) cells increased caspase-1 activity and production of IL-1ß by differentiated THP-1 cells. In the supernatant of FLC-4 cells with flutamide and bicalutamide, the heat shock protein (HSP) 40 or 60 was significantly increased. Addition of a carboxylesterase or a CYP inhibitor to the FLC-4 cells prevented release of HSPs from the FLC-4 cells. These results suggested that the reactive metabolites of flutamide and bicalutamide can cause the release of DAMPs from hepatocytes and activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by flutamide or bicalutamide, which in some patients, can cause immune-related adverse events.

Association between walking speed early after admission and all-cause death and/or readmission in patients with acute decompensated heart failure.

AIM: Patients with heart failure (HF) frequently experience decreased physical function, including walking speed. Slower walking speed is associated with poorer prognosis. However, most of these reports focused on patients with stable HF, and the relationship between walking speed in acute phase and clinical outcomes is unclear. Therefore, we aimed to investigate the associations between walking speed early after admission and clinical events in patients with acute decompensated HF (ADHF). METHODS AND RESULTS: We reviewed consecutive 1391 patients admitted due to ADHF. We measured walking speed the first time to walk on the ward more than 10 m after admission, and the speed within four days after admission was included in this study. The primary outcome was combined events (all-cause death and/or readmission due to HF). The follow-up period was up to one year from the discharge. The study population had a median age of 74 years (interquartile range [IQR]: 65-80 years), and 35.9% of patients were females. The median walking speed was 0.70 m/s (IQR: 0.54-0.88 m/s). Combined events occurred in 429 (30.8%) patients. Faster walking speed was independently associated with lower rate of combined events (adjusted hazard ratio per 0.1 m/s increasing: 0.951, 95% confidence interval:0.912-0.992). CONCLUSION: Faster walking speed within four days after admission was associated with favourable clinical outcomes in patients with ADHF. The results suggest that measuring walking speed in acute phase is useful for earlier risk stratification.

SARC-F predicts poor motor function, quality of life, and prognosis in older patients with cardiovascular disease and cognitive impairment.

OBJECTIVES: We investigated whether SARC-F scores were associated with motor function, quality of life (QOL) related to physical function, and prognosis in older patients with cardiovascular disease (CVD) and cognitive impairment. METHODS: This was a retrospective cross-sectional cohort study. The study population consisted of 408 patients with CVD (≥60 years old) who completed the SARC-F questionnaire and Mini-Cog, a cognitive function test, at discharge. Sarcopenia was defined as a total SARC-F score ≥ 4 points. Patients who were cognitively-preserved (Mini-Cog score ≥ 3 points) were excluded. Patients completed the handgrip strength, leg strength, usual gait speed, 6-minute walking distance, short physical performance battery score, and 36-item Short-Form Health Survey Physical Functioning (SF-36PF) tests before discharge. Associations of SARC-F with physical function, QOL, and prognoses (i.e., composite of all-cause death and emergency CVD rehospitalization and the number of CVD rehospitalizations) were investigated. RESULTS: Sarcopenia (SARC-F score ≥ 4 points) was associated with poorer motor function test outcomes and SF-36PF scores (all P < 0.001). The correlations remained significant after adjusting for comorbidities (e.g., anemia, prior heart failure, and renal dysfunction). Sarcopenia was also associated with a poorer prognosis (hazard ratio: 1.574; 95 % confidence interval [CI], 1.011-2.445) and an increased risk of CVD rehospitalization (incidence rate ratio: 1.911; 95 % CI, 1.312-2.782) after adjusting for comorbidities. CONCLUSIONS AND IMPLICATIONS: In older patients with CVD and cognitive impairment, the SARC-F questionnaire may be a simple and inexpensive tool for identifying patients with decreased motor function and a poor prognosis.

Prognostic Utility of Skeletal Muscle Mass Metrics in Patients With Heart Failure.

BACKGROUND: Sarcopenia is associated with risks of various adverse outcomes, and the assessment of skeletal muscle mass is necessary for its diagnosis. However, heart failure (HF) is a syndrome characterised by fluid retention, which affects muscle mass measurements. Different measurement methods have been reported to have different prognostic implications. We investigated the association between skeletal muscle mass metrics measured with the use of bioelectrical impedance analysis (BIA) and anthropometric measures and prognosis in patients with HF. METHODS: The findings of 869 consecutive patients with HF were reviewed. We investigated the skeletal muscle mass index (SMI) measured with the use of BIA, the mid-upper arm circumference (MUAC), the arm muscle circumference (AMC), and the calf circumference (CC), and the patients were divided into 3 groups according to the sex-specific tertiles of the skeletal muscle mass metrics. The end points were all-cause death and readmission due to HF. RESULTS: The high MUAC and AMC groups showed significantly better prognoses than their respective low groups (combined events: high MUAC group hazard ratio [HR] 0.559, 95% confidence interval [CI] 0.395-0.789 [P < 0.01]; high AMC group HR 0.505, 95% CI 0.359-0.710 [P < 0.01]), although high SMI and high CC were not associated with better prognoses. CONCLUSIONS: Among patients with HF, MUAC and AMC are more associated with prognosis than SMI and CC, which are recommended in preexisting sarcopenia guidelines. MUAC and AMC may also be useful measures in sarcopenia assessments.

Prognostic impact of the coexistence of hepato-renal dysfunction and frailty in patients with heart failure.

BACKGROUND: Complex multi-organ interactions such as coexistence of hepato-renal dysfunction in heart failure (HF) adversely affects patient prognosis. However, the association between liver/kidney dysfunction and frailty and effects of their coexistence on HF prognosis remain unclear. METHODS: This retrospective cohort study included 922 patients with HF (median age, 72 years; interquartile range: 62-79 years). All patients underwent hepato-renal function testing using the model for end-stage liver disease, excluding international normalized ratio (MELD-XI) score and frailty score. Frailty was measured using a composite of four markers: handgrip strength, gait speed, serum albumin, and activities of daily living status, combined into a total frailty score (range 0-12). Patients were assigned to a frailty score <5 (without frailty) or ≥5 (frailty) group. The multivariable logistic regression model was used to analyze the association between MELD-XI score and frailty; the prognostic value of high MELD-XI score and frailty coexistence was investigated. The endpoint was all-cause mortality. RESULTS: After adjusting for covariates and dividing by the median MELD-XI score, the high MELD-XI score group [odds ratio: 1.663, 95 % confidence interval (CI): 1.200-2.304, p = 0.002] was significantly associated with frailty, compared with the low MELD-XI score group. One hundred and fifty deaths occurred during follow-up (median, 2.13 years; interquartile range, 0.93-4.09 years). Patients in the high MELD-XI score/frailty group had a significantly higher mortality risk, even after adjusting for HF severity (hazard ratio: 4.326, 95 % CI: 2.527-7.403, p < 0.001). CONCLUSIONS: Hepato-renal dysfunction is associated with frailty in patients with HF, which affects patient prognosis. BRIEF SUMMARY: This study showed that hepato-renal dysfunction in patients with HF, as assessed by the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score, is associated with frailty, even after adjusting for factors involved in the frailty or severity of HF. Additionally, high MELD-XI score combined with frailty is associated with a poorer prognosis. These results suggest that hepato-renal dysfunction and frailty can be used for risk stratification in patients with HF.