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.

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.

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.

Nutrition Assessment and Education of Patients with Heart Failure by Cardiologists.

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

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.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

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.

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.

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.

Clinical characteristics and prognosis of patients with isolated cardiac sarcoidosis: Insights from the ILLUMINATE-CS study.

AIM: Data on the clinical features and prognosis of patients with isolated cardiac sarcoidosis (iCS) are limited. This study evaluated the clinical characteristics and prognostic impact of iCS. METHODS AND RESULTS: This was a secondary analysis of the ILLUMINATE-CS study, a multicentre, retrospective registry investigating the clinical characteristics and prognosis of cardiac sarcoidosis. iCS was diagnosed according to the 2016 Japanese Circulation Society (JCS) guidelines. Clinical characteristics and prognosis were compared between patients with iCS and systemic cardiac sarcoidosis (sCS). The primary outcome was a combined endpoint of all-cause death, hospitalization for heart failure, or fatal ventricular arrhythmia events. Among 475 patients with CS (mean age, 62.0 ± 10.9 years; female ratio, 59%) diagnosed by the JCS guidelines, 119 (25.1%) were diagnosed with iCS. Patients with iCS had a higher prevalence of a history of atrial fibrillation or hospitalization for heart failure, or lower left ventricular ejection fraction than those with sCS. During a median follow-up of 42.3 (interquartile range, 22.8-72.5) months, 141 primary outcomes (29.7%) occurred. Cox proportional hazard analysis revealed that iCS was a significant risk factor for the primary outcome in the unadjusted model (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.12-2.34; p = 0.011). However, this association was not retained after adjustment for other covariates (adjusted HR 1.27; 95% CI 0.86-1.88; p = 0.226). CONCLUSIONS: Patients with iCS had more impaired cardiovascular function at the time of diagnosis than those with sCS. However, iCS was not independently associated with poor prognosis after adjustment for prognostic factors.

A Case Report of Mixed-type Dyspnoea Diagnosed via Non-invasive and Invasive Cardiopulmonary Exercise Tests.

A gas exchange analysis with the cardiopulmonary exercise test is effective in discriminating non-cardiogenic components of limited exercise tolerance and is important for use in combination with the diastolic stress test. An 80-year-old woman with progressive exertional dyspnoea, hypertension, and untreated bronchial asthma was diagnosed with heart failure with a preserved ejection fraction by invasive testing. Diuretics were initiated, which resulted in partial symptom improvement. A subsequent non-invasive test revealed a reduced breathing reserve, suggesting exertional dyspnoea complications linked to lung disease. Bronchodilators were administered, which further improved the symptoms.

Prevalence and prognostic value of atrial fibrillation in patients with cardiac sarcoidosis.

Aims: The prognostic value of the presence of atrial fibrillation (AF) in patients at the time of cardiac sarcoidosis (CS) diagnosis is unknown. This study aimed to investigate the association between AF at the time of CS diagnosis and patient prognosis. Methods and results: This study is a post-hoc analysis of Illustration of the Management and Prognosis of Japanese Patients with CS, a multicentre, retrospective observational study that evaluated the clinical characteristics and prognosis of patients with CS. The primary endpoint was the combined endpoint of all-cause death and hospitalization due to heart failure. After excluding patients with missing data about AF status, 445 patients (62 ± 11 years, 36% males) diagnosed with CS according to the Japanese current diagnostic guideline were analysed. Compared to patients without AF, patients with AF (n = 46, 10%) had higher levels of brain natriuretic peptide and a higher prevalence of heart failure hospitalizations. During a median follow-up period of 3.2 years (interquartile range, 1.7-5.8 years), 80 primary endpoints were observed. Kaplan-Meier curve analysis indicated that concomitant AF at the time of diagnosis was significantly associated with a high incidence of primary endpoints (log-rank P = 0.002). This association was retained after adjusting for known risk factors including log-transformed brain natriuretic peptide levels and left ventricular ejection fractions [hazard ratio, 1.96 (95% confidence interval, 1.05-3.65); P = 0.035]. Conclusion: The presence of AF at the time of CS diagnosis is associated with higher incidence of all-cause death and heart failure hospitalization.

Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

BACKGROUND AND AIMS: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. METHODS AND RESULTS: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360). CONCLUSION: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality.

Usefulness of HANBAH Score in Japanese Patients With Acute Heart Failure.

The HANBAH score is a novel simple risk score consisting of hemoglobin level, age, sodium (N) level, blood urea nitrogen level, atrial fibrillation, and high-density lipoprotein. We aimed to validate this score in an external population. This retrospective study included 744 patients hospitalized for acute heart failure between 2015 and 2019. Each of the following criteria was scored as 1 point: hemoglobin level (<13.0 g/L for men and <12.0 g/L for women), atrial fibrillation, age (>70 years), serum blood urea nitrogen level (>26 mg/100 ml for men and >28 mg/100 ml for women), serum high-density lipoprotein level (<25 mg/100 ml), and serum sodium level (<135 mg/100 ml). HANBAH scores were available for 736 patients (age, 75 ± 13 years; 60% male; reduced [<40%] and preserved ejection fraction [≥50%]: 35% and 49%, respectively). All-cause death during follow-up, a composite of death and heart failure rehospitalization, and in-hospital death were observed in 173, 274, and 51 patients, respectively. The HANBAH score was significantly associated with these end points after adjustment for covariates (adjusted hazard ratio 1.38 [95% confidence interval 1.16 to 1.64], p <0.001; 1.27 [1.11 to 1.45], p <0.001; and 1.66 [1.18 to 2.33], p <0.001, respectively). Receiver operating characteristic and net reclassification improvement analyses showed that the HANBAH score performed significantly better than AHEAD (atrial fibrillation, hemoglobin [anemia], elderly, abnormal renal parameters, diabetes mellitus) and AHEAD-U (AHEAD with uric acid) scores and similar to the multi-domain ACUTE HF score for all end points. In conclusion, the HANBAH score showed powerful risk stratification in this external Japanese cohort. Despite its simplicity, it performed better than other simple risk scores and similar to a multidomain risk score.

Sex differences in clinical characteristics and prognosis of patients with cardiac sarcoidosis.

OBJECTIVE: Owing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). METHODS: This study was a secondary analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis registry-a retrospective multicentre registry that enrolled patients with CS between 2001 and 2017. The primary outcome was potentially fatal ventricular arrhythmia events (pFVAEs)-a composite of sudden cardiac death, sustained ventricular tachycardia lasting >30 s, ventricular fibrillation or the requirement for implantable cardioverter defibrillator therapy. RESULTS: Of the 512 participants (mean age±SD 61.6±11.4 years), 329 (64.2%) were females. Both sexes had peak ages of 60-64 years at diagnosis. Male patients were younger and had a higher prevalence of coronary artery disease and lower left ventricular ejection fraction than female patients. During a median follow-up of 3 years (IQR 1.6-5.6), pFVAEs were observed in 99 patients, with males having a significantly higher risk than females (p=0.002). This association was retained even after adjustment for other risk factors for pFVAEs, including left ventricular ejection fraction (adjusted HR 1.80; 95% CI 1.08 to 3.01, p=0.025). CONCLUSION: Approximately two-thirds of patients with CS were females, with a peak age of approximately 60 years at clinical diagnosis in both sexes; male patients were younger than female patients. Male patients had a significantly higher risk of pFVAEs than female patients. TRIAL REGISTRATION NUMBER: UMIN000034974.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

Prevalence and prognostic impact of the coexistence of cachexia and sarcopenia in older patients with heart failure.

BACKGROUND: No study with an adequate patients' number has examined the relationship/overlap between sarcopenia and cachexia. We examined the prevalence of the overlap and prognostic implications of sarcopenia and cachexia in older patients with heart failure using well-accepted definitions. METHODS: This was a post-hoc sub-analysis of the FRAGILE-HF study, a prospective, multicenter, observational study conducted at 15 hospitals in Japan. In total, 905 hospitalized older patients were classified into four groups based on the presence or absence of cachexia and/or sarcopenia, which were defined according to the Evans and Asian Working Group for Sarcopenia criteria revised in 2019, respectively. The primary endpoint was 2-year all-cause mortality. RESULTS: Cachexia and sarcopenia prevalence rates were 32.7% and 22.7%, respectively. Patients were classified into the non-cachexia/non-sarcopenia (55.7%), cachexia/non-sarcopenia (21.7%), non-cachexia/sarcopenia (11.6%), and cachexia/sarcopenia (11.0%) groups. During the 2-year follow-up period after discharge, 158 (17.5%) all-cause deaths (124 cardiovascular deaths [CVD] and 34 non-CVD) were observed. The cachexia/sarcopenia group had the lowest body fat mass and exhibited significantly higher mortality rates (log-rank P < 0.001). Cox proportional hazard analysis revealed that cachexia/sarcopenia was an independent prognostic factor after adjusting for known prognostic factors (versus non-cachexia/non-sarcopenia: hazard ratio, 2.78; 95% confidence interval, 1.80-4.29; P < 0.001). Neither cachexia/non-sarcopenia nor non-cachexia/sarcopenia were significantly associated with all-cause mortality compared with non-cachexia/non-sarcopenia. CONCLUSIONS: Cachexia and sarcopenia are prevalent among older hospitalized patients with heart failure; nonetheless, the overlap is not as prominent as previously expected. The presence of cachexia and sarcopenia is a risk factor for all-cause mortality.

Prognostic implications of six-minute walking distance in patients with heart failure with preserved ejection fraction.

BACKGROUND: The incremental prognostic value of the six-minute walking test over conventional risk factors has not been evaluated in an adequate number of patients with heart failure with preserved ejection fraction (HFpEF). Therefore, we aimed to examine its prognostic significance using data from the FRAGILE-HF study. METHODS AND RESULTS: A total of 513 older patients who were hospitalized for worsening heart failure were examined. Patients were classified according to the tertiles of six-minute walking distance (6MWD): T1 (<166 m), T2 (166-285 m), and T3 (≥285 m). During the 2-year follow-up period after discharge, 90 all-cause deaths occurred. Kaplan-Meier curves showed that the T1 group had significantly higher event rates than the other groups (log-rank p = 0.007). Cox proportional hazard analysis revealed that the T1 group was independently associated with lower survival, even after adjusting for conventional risk factors (T3: hazard ratio 1.79, 95% confidence interval 1.02-3.14, p = 0.042). The addition of the 6MWD to the conventional prognostic model showed a statistically significant incremental prognostic value (net reclassification improvement 0.27, 95% confidence interval 0.04-0.49; p = 0.019). CONCLUSIONS: The 6MWD is associated with survival in patients with HFpEF and has an incremental prognostic value over conventional well-validated risk factors.

Blood pressure in heart failure management and prevention.

Hypertension is a leading cause of heart failure and other cardiovascular diseases. Its role in the pathogenesis of heart failure with reduced ejection fraction (HFrEF) differs from that in heart failure with preserved ejection fraction (HFpEF). Moreover, rigorous blood pressure control may reduce the incidence of heart failure. However, once heart failure develops, prognosis is affected by blood pressure, which may differ between patients with and without heart failure. Therefore, the association between guideline-directed medical therapy (GDMT) for heart failure and its uptitration must be considered for blood pressure management and should not be overlooked. Heart failure medications affect the blood pressure and efficacy per baseline blood pressure value. This review discusses the potential mechanisms by which hypertension leads to HFrEF or HFpEF, the impact of hypertension on incident heart failure, and the recommended approaches for blood pressure management in patients with heart failure. Comparison between patients with and without heart failure regarding blood pressure The association between CV events and SBP is linear in patients without heart failure; however, it becomes J-shaped or inverse linear in those with heart failure. The management of BP, including optimal BP or pharmacotherapy, differs between the two populations. ACEi angiotensin-converting enzyme inhibitors, ARB angiotensin II receptor blockers; ARNi angiotensin receptor-neprilysin inhibitors, BB beta-blockers, BP blood pressure, CV cardiovascular, DASH Dietary Approaches to Stop Hypertension, GDMT guideline-directed medical therapy, HF heart failure, HFrEF heart failure with reduced ejection fraction, MRA mineralocorticoid receptor antagonists, SBP systolic blood pressure, SGLT2i sodium-glucose cotransporter 2 inhibitors.

External validation of the ACUTE HF score for risk stratification in acute heart failure.

BACKGROUND: The ACUTE HF score is a simple risk score that predicts the prognosis of patients with acute heart failure (HF) using clinical and echocardiographic parameters. As this score was developed for a small European population, we aimed to validate this score in an external population. METHODS AND RESULTS: This retrospective observational cohort analysis included patients hospitalized with acute HF during 2015-2019. Of 744 patients, 703 patients with available ACUTE HF scores were analyzed (75 ± 13 years; 61% male; left ventricular ejection fraction [LVEF] 49 ± 17%). Approximately one-third (34.4%) of the patients had reduced LVEF (<40%), and 51.4% exhibited preserved LVEF (≥50%). During a median follow-up of 452 days, primary and secondary outcomes were observed in 110 and 204 patients, respectively. The ACUTE HF score successfully stratified patients for primary (all-cause mortality) and secondary endpoints (a composite of all-cause mortality and heart failure rehospitalization) in Kaplan-Meier analyses (log-rank test, P < 0.001). Multivariable Cox proportional hazards models showed that the score was significantly independently associated with both primary and secondary endpoints after adjusted by covariates (P < 0.001). CONCLUSION: We validated the risk prediction ability of ACUTE HF score in an Asian population. This score may be applicable in clinical practice.