Prognostic Value of Objective Social Isolation and Loneliness in Older Patients With Heart Failure: Subanalysis of FRAGILE-HF and Kitasato Cohort.

BACKGROUND: Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure. METHODS AND RESULTS: This study was conducted using the FRAGILE-HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale-6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale-6 was below the median in the FRAGILE-HF. The primary outcome was 1-year death. Overall, 1232 and 405 patients in the FRAGILE-HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE-HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1-year follow-up, 149 and 31 patients died in the FRAGILE-HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1-year death after adjustment for conventional risk factors in the FRAGILE-HF. These findings were consistent with the validation cohort. CONCLUSIONS: Objective SI assessed using the Lubben Social Network Scale-6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Oral nutritional supplements in older outpatients with heart failure: rationale and design of the ALIMENT-HF trial.

AIMS: The ALIMENT-HF trial aims to determine whether high-calorie and high-protein oral nutritional supplements (ONS) are safe and beneficial for older adult outpatients with heart failure (HF). METHODS AND RESULTS: This multicentre, single-arm, interventional pilot trial is designed to evaluate the tolerance, efficacy, and safety of ONS in older adult outpatients with chronic HF, malnutrition, and anorexia. In total, 80 outpatients with HF regardless of their left ventricular ejection fraction will be treated with ONS, including high-energy (900 kcal/day) and high protein (36 g/day) supplementation, at eight sites in Japan. Inclusion criteria are as follows: age, ≥65 years; outpatients receiving maximally tolerated guideline-directed medical therapy for HF and without change in their diuretic dosage during the last 3 months; outpatients at risk of malnutrition, defined as a Malnutrition Universal Screening Tool score ≥1 point, and anorexia, defined using a Simplified Nutritional Appetite Questionnaire for the Japanese Elderly (SNAQ-JE) score of ≤14 points. Nutritional intervention will continue for up to 120 days, with an observational period lasting for a further 60 days. The primary outcome is a change in body weight between baseline and day 120. CONCLUSIONS: The ALIMENT-HF trial will evaluate the tolerance, efficacy, and safety of high-calorie and high-protein-rich ONS in older outpatients with HF co-morbid with malnutrition and anorexia and will provide insightful information for future randomized controlled trials.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death. Key findings: Only a small number of older patients with heart failure have trouble breathing when they bend forward.However, those who do have this problem are more likely to die.

High cell density cultivation of Corynebacterium glutamicum by deep learning-assisted medium design and the subsequent feeding strategy.

To improve the cell productivity of Corynebacterium glutamicum, its initial specific growth rate was improved by medium improvement using deep neural network (DNN)-assisted design with Bayesian optimization (BO) and a genetic algorithm (GA). To obtain training data for the DNN, experimental design with an orthogonal array was set up using a chemically defined basal medium (GC XII). Based on the cultivation results for the training data, specific growth rates were observed between 0.04 and 0.3/h. The resulting DNN model estimated the test data with high accuracy (R2test ≥ 0.98). According to the validation cultivation, specific growth rates in the optimal media components estimated by DNN-BO and DNN-GA increased from 0.242 to 0.355/h. Using the optimal media (UCB_3), the specific growth rate, along with other parameters, was evaluated in batch culture. The specific growth rate reached 0.371/h from 3 to 12 h, and the dry cell weight was 28.0 g/L at 22.5 h. From the cultivation, the cell yields against glucose, ammonium ion, phosphate ion, sulfate ion, potassium ion, and magnesium ion were calculated. The cell yield calculation was used to estimate the required amounts of each component, and magnesium was found to limit the cell growth. However, in the follow-up fed-batch cultivation, glucose and magnesium addition was required to achieve the high initial specific growth rate, while appropriate feeding of glucose and magnesium during cultivation resulted in maintaining the high specific growth rate, and obtaining a cell yield of 80 g/Lini.

Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

BACKGROUND: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. METHODS: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. RESULTS: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P<0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths. CONCLUSIONS: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.

Elevated Leukocyte Count and Platelet-Derived Thrombogenicity Measured Using the Total Thrombus-Formation Analysis System in Patients with ST-Segment Elevation Myocardial Infarction.

AIMS: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. METHODS: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. RESULTS: Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (ß=0.26, p=0.0065). CONCLUSIONS: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

Prognostic impact of MitraScore in elderly Asian patients with heart failure: sub-analysis of FRAGILE-HF.

AIMS: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. METHODS AND RESULTS: We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE-HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all-cause deaths, and the secondary endpoints were the composite of all-cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2-4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low-, moderate-, and high-risk groups based on the MitraScore, respectively. During a follow-up of 2 years, 226 all-cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan-Meier analysis (P < 0.001 for all). In multivariate analyses, MitraScore was significantly associated with all endpoints after covariate adjustments [adjusted hazard ratio (HR) (95% confidence interval): 1.22 (1.10-1.36), P < 0.001 for all-cause deaths; adjusted HR 1.17 (1.09-1.26), P < 0.001 for combined endpoints; and adjusted HR 1.24 (1.10-1.39), P < 0.001 for cardiovascular deaths]. The Hosmer-Lemeshow plot showed good calibration for all endpoints. The net reclassification improvement (NRI) analyses revealed that the MitraScore performed significantly better than other manually calculatable risk scores of HF: the GWTG-HF risk score, the BIOSTAT compact model, the AHEAD score, the AHEAD-U score, and the HANBAH score for all-cause and cardiovascular deaths, with respective continuous NRIs of 0.20, 0.22, 0.39, 0.39, and 0.29 for all-cause mortality (all P-values < 0.01) and 0.20, 0.22, 0.42, 0.40, and 0.29 for cardiovascular mortality (all P-values < 0.02). CONCLUSIONS: MitraScore developed for patients undergoing TEER also showed strong discriminative power in HF patients. MitraScore was superior to other manually calculable simple risk scores and might be a good choice for risk assessment in clinical practice for patients receiving TEER and those with HF.

Optimization of medium components for protein production by Escherichia coli with a high-throughput pipeline that uses a deep neural network.

To optimize rapidly the medium for green fluorescent protein expression by Escherichia coli with an introduced plasmid, pRSET/emGFP, a single-cycle optimization pipeline was applied. The pipeline included a deep neural network (DNN) and mathematical optimization algorithms with simultaneous optimization of 18 medium components. To evaluate the DNN data sampling method, two methods, orthogonal array (OA) and Latin hypercube sampling (LHS), were used to design 64 initial media for each sampling method. The OA- and LHS-based data sampling resulted in green fluorescent protein fluorescence intensities of 0.088 × 103-1.85 × 104 and 3.30 × 103-1.50 × 104, respectively. Fifty DNN models were built using the OA and LHS datasets. Hold-out validation was performed using 15 % test of OA and LHS data. Mean square errors of the DNN models were 0.015-0.64, indicating the estimation accuracies were sufficient. However, the sensitivities of components in the DNN models varied and were grouped into six major classes by the index of k-means clustering. A representative model was selected for each class. Mathematical optimization algorithms using Bayesian optimization and genetic algorithm were applied to the representative models, and representative optimized medium (OM) compositions were selected by k-means clustering from the proposed OMs. A total of 54 OMs were obtained from the OA and LHS datasets. In the validating cultivation, the best OMs of OA and LHS were 2.12-fold and 2.13-fold higher, respectively, than those of the learning data.

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.

A machine-learning-based prediction of non-home discharge among acute heart failure patients.

BACKGROUND: Scarce data on factors related to discharge disposition in patients hospitalized for acute heart failure (AHF) were available, and we sought to develop a parsimonious and simple predictive model for non-home discharge via machine learning. METHODS: This observational cohort study using a Japanese national database included 128,068 patients admitted from home for AHF between April 2014 and March 2018. The candidate predictors for non-home discharge were patient demographics, comorbidities, and treatment performed within 2 days after hospital admission. We used 80% of the population to develop a model using all 26 candidate variables and using the variable selected by 1 standard-error rule of Lasso regression, which enhances interpretability, and 20% to validate the predictive ability. RESULTS: We analyzed 128,068 patients, and 22,330 patients were not discharged to home; 7,879 underwent in-hospital death and 14,451 were transferred to other facilities. The machine-learning-based model consisted of 11 predictors, showing a discrimination ability comparable to that using all the 26 variables (c-statistic: 0.760 [95% confidence interval, 0.752-0.767] vs. 0.761 [95% confidence interval, 0.753-0.769]). The common 1SE-selected variables identified throughout all analyses were low scores in activities of daily living, advanced age, absence of hypertension, impaired consciousness, failure to initiate enteral alimentation within 2 days and low body weight. CONCLUSIONS: The developed machine learning model using 11 predictors had a good predictive ability to identify patients at high risk for non-home discharge. Our findings would contribute to the effective care coordination in this era when HF is rapidly increasing in prevalence.

The barriers to interprofessional care for cancer cachexia among Japanese healthcare providers: A nationwide survey.

BACKGROUND: Cancer cachexia is a severe complication of advanced malignancy, with few therapeutic options. To promote interprofessional care for cancer cachexia, healthcare providers' needs should be addressed in detail. This pre-planned subgroup analysis of the Global Educational Needs Evaluation: a systemic interprofessional study in cancer cachexia (GENESIS-CC) survey aimed to identify barriers to interprofessional care of cancer cachexia in Japan. METHODS: A nationwide survey was electronically conducted for healthcare providers in oncological or general healthcare facilities from January to March 2021 in Japan. The Japanese Regional Advisory Board developed a barrier scoring system with 33 from the 58 original survey items to quantify six domains of barriers: (1) lack of confidence, (2) lack of knowledge, (3) barriers in personal practice, (4) barriers in perception, (5) barriers in team practice and (6) barriers in education. The largest possible barrier score was set at 100 points. We compared the scores by profession. RESULTS: A total of 1227 valid responses were obtained from 302 (24.6%) physicians, 252 (20.5%) pharmacists, 236 (19.2%) nurses, 218 (17.8%) dietitians, 193 (15.7%) rehabilitation therapists and 26 (2.0%) other professionals. Overall, 460 (37.5%) were not very or at all confident about cancer cachexia care, 791 (84.1%) agreed or strongly agreed that care was influenced by reimbursement availability and 774 (81.9%) did not have cancer cachexia as a mandatory curriculum. The largest mean barrier score (± standard deviation) was 63.7 ± 31.3 for education, followed by 55.6 ± 21.8 for team practice, 43.7 ± 32.5 for knowledge, 42.8 ± 17.7 for perception and 36.5 ± 16.7 for personal practice. There were statistically significant interprofessional differences in all domains (P < 0.05), especially for pharmacists and nurses with the highest or second highest scores in most domains. CONCLUSIONS: There is a need to improve the educational system and team practices of cancer cachexia for most Japanese healthcare providers, especially pharmacists and nurses. Our study suggests the need to reform the mandatory educational curriculum and reimbursement system on cancer cachexia to promote interprofessional care for cancer cachexia in Japan.

Association and Prognostic Value of Multidomain Frailty Defined by Cumulative Deficit and Phenotype Models in Patients With Heart Failure.

BACKGROUND: Frailty is associated with a poor prognosis in older patients with heart failure (HF). However, multidomain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF. METHODS: We retrospectively analyzed FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥ 65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality. RESULTS: Among 1027 patients with HF (median age, 81 years; male, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the 2-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score plus log B-type natriuretic peptide (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37; P = 0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P = 0.034). CONCLUSIONS: A higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with pre-existing risk factors in older patients with HF.

Early mobilization for acute heart failure: A scoping and a systematic review.

Early mobilization of hospitalized patients is beneficial under certain circumstances. This has been applied in clinical practice for patients with acute heart failure (HF). However, its current definition, effectiveness, and safety are not well established. This review aimed to clarify the current definition of "early mobilization," and summarize its effectiveness and safety in acute HF. We conducted a scoping review to define early mobilization (Part 1) and a systematic review and meta-analysis (Part 2) to evaluate its effectiveness and safety. For Part 1, we searched MEDLINE (Ovid), and for Part 2, we searched the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), Embase (ProQuest Dialog), CINAHL, and PEDro. We included 12 studies in Part 1 and defined early mobilization as protocol-based interventions or walking within 3 days of admission. Based on this definition, two observational studies were included in Part 2, with no randomized controlled trials. Early mobilization may result in a large reduction in the readmission rate compared with that of the control (two studies, 283 participants: odds ratio 0.25, 95 % confidence interval 0.14 to 0.42; I2 = 0 %; low certainty evidence). We could not define frequency, intensity, or quantity because many of the included studies did not describe them. In conclusions, our review suggests that early mobilization, defined as protocol-based interventions or walking within 3 days of admission, may be associated with a low readmission rate in patients with acute HF. Future studies are essential, to investigate the causal relationship between early mobilization and possible outcomes.

Impact of Low-Density Lipoprotein Cholesterol Levels at Acute Coronary Syndrome Admission on Long-Term Clinical Outcomes.

AIM: Low-density lipoprotein cholesterol (LDL-C) level reduction is highly effective in preventing the occurrence of a cardiovascular event. Contrariwise, an inverse association exists between LDL-C levels and prognosis in some patients with cardiovascular diseases-the so-called "cholesterol paradox." This study aimed to investigate whether the LDL-C level on admission affects the long-term prognosis in patients who develop acute coronary syndrome (ACS) and to examine factors associated with poor prognosis in patients with low LDL-C levels. METHODS: We enrolled 410 statin-naïve patients with ACS, whom we divided into low- and high-LDL-C groups based on an admission LDL-C cut-off (obtained from the Youden index) of 122 mg/dL. Endothelial function was assessed using the reactive hyperemia index 1 week after statin initiation. The primary composite endpoint included all-cause death, as well as myocardial infarction and ischemic stroke occurrences. RESULTS: During a median follow-up period of 6.1 years, 76 patients experienced the primary endpoint. Multivariate Cox regression analysis revealed that patients in the low LDL-C group had a 2.3-fold higher risk of experiencing the primary endpoint than those in the high LDL-C group (hazard ratio, 2.34; 95% confidence interval, 1.29-4.27; p=0.005). In the low LDL-C group, slow gait speed (frailty), elevated chronic-phase high-sensitivity C-reactive protein levels (chronic inflammation), and endothelial dysfunction were significantly associated with the primary endpoint. CONCLUSIONS: Patients with low LDL-C levels at admission due to ACS had a significantly worse long-term prognosis than those with high LDL-C levels; frailty, chronic inflammation, and endothelial dysfunction were poor prognostic factors.

Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia.

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Prognostic impact of cachexia by multi-assessment in older adults with heart failure: FRAGILE-HF cohort study.

BACKGROUND: Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults. METHODS: This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis. RESULTS: Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74-86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173-1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048-2.023; P = 0.025) and 1.561 (95% CI, 1.086-2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095-2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052-1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895-1.471; P = 0.277) and all-cause mortality. CONCLUSIONS: Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

High-intensity interval training versus moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis.

The effects of high-intensity interval training (HIIT) in patients with heart failure (HF) remain controversial. This systematic review and meta-analysis aimed to examine the efficacy of HIIT versus moderate-intensity continuous aerobic training (MCT) on exercise tolerance in patients with HF. We searched for studies published up to 4 March 2022 in Embase, MEDLINE, PubMed, and the Cochrane Library with no limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. We identified 15 randomized controlled trials with 557 patients. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; participants = 557; studies = 15; I2 = 65.7%; very low-quality evidence). The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the difference in peak VO2 between HIIT and MCT was inversely associated with body mass index (r = - 0.508, p = 0.028, 95% confidence interval - 0.95 to - 0.07). Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with HF. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

Association between sarcopenia and exercise capacity in patients with pulmonary hypertension without left heart disease.

BACKGROUND: Pulmonary hypertension (PH) has recently been described as a complex clinical syndrome affecting multiple organ systems, including the heart, lungs, and skeletal muscle, each of which plays an important role in exercise capacity. However, the relationship between exercise capacity and skeletal muscle abnormalities in patients with PH has not been fully elucidated. METHODS: We retrospectively analysed the exercise capacity and measures of skeletal muscle of 107 patients with PH without left heart disease (mean age 63 ± 15 years, 32.7% males, n = 30/6/66/5 in the clinical classification Group 1/3/4/5). RESULTS: Sarcopenia, low appendicular skeletal muscle mass index, low grip strength, and slow gait speed, determined by international criteria, were found in 15 (14.0%), 16 (15.0%), 62 (57.9%), and 41 (38.3%) patients, respectively. The mean 6-min walk distance of all patients was 436 ± 134 m and was independently associated with sarcopenia (standardised ß = -0.292, p < 0.001). All patients with sarcopenia showed reduced exercise capacity defined as 6-min walk distance < 440 m. Multivariable logistic regression analysis showed that each of the components of sarcopenia was associated with reduced exercise capacity (adjusted odds ratio and 95% confidence interval of appendicular skeletal muscle mass index: 0.39 [0.24-0.63] per 1 kg/m2, p = 0.006, grip strength: 0.83 [0.74-0.94] per 1 kg, p = 0.003, and gait speed: 0.31 [0.18-0.51] per 0.1 m/s, p < 0.001). CONCLUSIONS: Sarcopenia and its components are associated with reduced exercise capacity in patients with PH. A multifaceted evaluation may be important in the management of reduced exercise capacity in patients with PH.