AimsHeart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non‐alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid.Methods and resultsWe performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first–fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B‐type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B‐type natriuretic peptide, and NFS (P < 0.001 each). In the follow‐up period (mean 1107 days), 93 deaths occurred. All‐cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all‐cause mortality in the HFpEF patients.ConclusionsNFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all‐cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients.

ObjectiveLiver dysfunction due to heart failure (HF) is known as congestive hepatopathy. It has recently been reported that liver stiffness assessed by transient elastography reflects increased central venous pressure. The Fibrosis-4 (FIB4) index (age (years) × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)) is expected to be useful for evaluating liver stiffness in patients with non-alcoholic fatty liver disease. We aimed to investigate the impact of the FIB4 index on HF prognosis, with consideration for liver fibrosis markers and underlying cardiac function.MethodsConsecutive 1058 patients with HF who were admitted to our hospital were divided into three groups based on their FIB4 index: first (FIB4 index <1.72, n=353), second (1.72≤FIB4 index <3.01, n=353) and third tertiles (3.01≤FIB4 index, n=352). We prospectively followed for all-cause mortality.ResultsDuring the follow-up period (mean 1047 days), 246 deaths occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from the first to third groups (12.2%, 21.0% and 36.6%, p<0.01). In the Cox proportional hazard analysis, FIB4 index was an independent predictor of all-cause mortality in patients with HF (p<0.05). In comparisons of laboratory and echocardiographic findings, the third tertile had higher levels of type IV collagen 7S, procollagen type III peptide, hyaluronic acid, left atrial volume, mitral valve E/e’, inferior vena cava diameter and right atrial end systolic area (p<0.01, respectively).ConclusionThe FIB4 index, a marker of liver stiffness, is associated with higher all-cause mortality in patients with HF.

BackgroundThe Get With the Guidelines–Heart Failure (GWTG‐HF) risk score was developed using American Heart Association GWTG‐HF program data and predicts in‐hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG‐HF risk score in patients with HF after discharge.Methods and ResultsWe examined the GWTG‐HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG‐HF risk score (low, moderate, and high score groups). The plasma B‐type natriuretic peptide level significantly increased with increasing GWTG‐HF risk score severity (median values of B‐type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all‐cause deaths and 407 (28.0%) cardiac events in follow‐up periods. A Kaplan‐Meier survival curve demonstrated that event rates of all‐cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG‐HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction <50%) patients. The multivariable Cox proportional hazard regression analysis demonstrated that the GWTG‐HF risk score was one of the significant predictors of all‐cause mortality and cardiac events (all‐cause mortality: hazard ratio, 1.537, 95% confidence interval, 1.172–2.023; cardiac events: hazard ratio, 1.584, 95% confidence interval, 1.344–1.860, per 10‐point increase of GWTG‐HF score).ConclusionsThe GWTG‐HF risk score is a useful multivariable score model for several years after hospitalization in patients with HF in a Japanese population.

Abstract. annexin a1 (anxa1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. In the present study, we investigated the expression of anxa1 in gastric and colon cancer, and analyzed the relationship between ANXA1 expression and clinicopathological factors. anxa1 mrna expression in gastric and colon cancer tissues was not significantly changed compared to that in normal tissues. When anxa1 protein expression was evaluated by immunohistochemical staining, ANXA1 expression was observed in 76 of 135 cases of gastric cancer (56.3%), and correlations were found between ANXA1 expression and depth of wall invasion (P<0.001), lymphatic invasion (P=0.023), venous invasion (P=0.002), lymph node metastasis (P=0.001) and UICC stage (P<0.001). Disease-specific survival rate was significantly lower in cases with ANXA1 expression compared to that in cases without (P=0.0053). In colon cancer, ANXA1 expression was detected in 61 of 210 cases (29.0%) and correlations were found with gender (P=0.038), lymphatic invasion (P=0.011), venous invasion (P=0.023), lymph node metastasis (P=0.042) and UICC stage (P=0.041). The disease-specific survival rate tended to be lower in cases with ANXA1 expression, although the differences were not statistically significant (P=0.6984). Our results indicate that up-regulated ANXA1 expression is involved in cancer invasion and lymph node metastasis. Furthermore, high levels of anxa1 expression were implicated in poor prognosis of patients. ANXA1 may be applicable as a prognostic biomarker in gastric and colon cancer, and a potential target for treatment.

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.