Hirotake Okazaki

The prognostic impact of uric acid in patients with severely decompensated acute heart failure

BACKGROUND The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute HF (AHF) patients are not well understood. METHODS AND RESULTS Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA≤7.0mg/dl, n=495) or a high UA group (UA>7.0mg/dl, n=394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p=0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%CI: 1.010-2.397, p=0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients. CONCLUSIONS The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF.

New scoring system (APACHE-HF) for predicting adverse outcomes in patients with acute heart failure: Evaluation of the APACHE II and Modified APACHE II scoring systems

BACKGROUND No scoring system for assessing acute heart failure (AHF) has been reported. METHODS AND RESULTS Data for 824 AHF patients were analyzed. The subjects were divided into an alive (n=750) and a dead group (n=74). We constructed a predictive scoring system based on eight significant APACHE II factors in the alive group [mean arterial pressure (MAP), pulse, sodium, potassium, hematocrit, creatinine, age, and Glasgow Coma Scale (GCS); giving each one point], defined as the APACHE-HF score. The patients were assigned to five groups by the APACHE-HF score [Group 1: point 0 (n=70), Group 2: points 1 and 2 (n=343), Group 3: points 3 and 4 (n=294), Group 4: points 5 and 6 (n=106), and Group 5: points 7 and 8 (n=11)]. A higher optimal balance was observed in the APACHE-HF between sensitivity and specificity [87.8%, 63.9%; area under the curve (AUC)=0.779] at 2.5 points than in the APACHE II (47.3%, 67.3%; AUC=0.558) at 17.5 points. The multivariate Cox regression model identified belonging to Group 5 [hazard ratio (HR): 7.764, 95% confidence interval (CI) 1.586-38.009], Group 4 (HR: 6.903, 95%CI 1.940-24.568) or Group 3 (HR: 5.335, 95%CI 1.582-17.994) to be an independent predictor of 3-year mortality. The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and HF events (death, readmission-HF), in Group 5 and Group 4 than in the other groups, in Group 3 than in Group 2 or Group 1, and in Group 2 than in Group 1. CONCLUSIONS The new scoring system including MAP, pulse, sodium, potassium, hematocrit, creatinine, age, and GCS (APACHE-HF) can be used to predict adverse outcomes of AHF.

Clinical significance of acid-base balance in an emergency setting in patients with acute heart failure.

BACKGROUND AND PURPOSE The role of an arterial blood gas analysis in acute heart failure (AHF) remains unclear. The acid-base balance could help to treat AHF, and it might help to distinguish different types of AHF, while it might be associated with the AHF prognosis. The present study was conducted to determine the relationship between the arterial blood gas sample at the time of hospital admission and clinical findings on admission, outcomes. METHODS AND RESULTS Six hundred twenty-one patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to an alkalosis group (n=99, pH>7.45), normal group (n=178, 7.35≤ pH≤ 7.45), and acidosis group (n=344, pH<7.35). The clinical findings on admission and outcomes (in-hospital mortality and any-cause death within 2 years) were compared between the three groups. The white blood cell counts (WBC), serum levels of total protein, albumin, and glucose were significantly lower, and the serum levels of C-reactive protein (CRP) and total bilirubin were significantly higher in the alkalosis group. Patients with orthopnea were significantly fewer, and the systolic blood pressure (SBP) and heart rate (HR) were significantly lower in the alkalosis group. The results of a multivariate logistic regression model for in-hospital mortality found that alkalosis was an independent risk factor (p=0.017, odds ratio: 2.589; 95% confidence interval: 1.186-5.648). The Kaplan-Meier curves showed the prognosis for any-cause death to be significantly poorer in the alkalosis group than in the normal group (p=0.026). CONCLUSIONS The factors associated with alkalosis AHF were high CRP, bilirubin, and low WBC, glucose, total protein, and albumin. The patients with alkalosis AHF were less likely to have orthopnea with low SBP and HR. They suggested that the patients with alkalosis AHF might have experienced AHF for a few days and were associated with high mortality.

Serum Heart-Type Fatty Acid-Binding Protein Level Can Be Used to Detect Acute Kidney Injury on Admission and Predict an Adverse Outcome in Patients With Acute Heart Failure

BACKGROUND Different mechanisms of acute kidney injury (AKI) may exist for acute heart failure (AHF) patients compared with other patients. METHODS AND RESULTS We analyzed data from 282 patients with AHF. The biomarkers were measured within 30 min of admission. Patients were assigned to a no-AKI (n=213) or AKI group (Class R (n=49), Class I (n=15) or Class F (n=5)) using the RIFLE classifications on admission. We evaluated the relationships between the biomarkers and AKI, in-hospital mortality, all-cause death and HF events (HF re-admission, all-cause death) within 90 days. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the AKI than in the no-AKI group, and the predictive biomarker for AKI was s-HFABP (odds ratio: 6.709; 95% confidence interval: 3.362-13.391). s-HFABP demonstrated an optimal balance between sensitivity and specificity (71.0%, 79.3%; area under the receiver-operating characteristic curve [AUC]=0.790) at 22.8 ng/ml for AKI, at 22.8 ng/ml for Class I/F (90.0%, 71.4%; AUC=0.836) and at 21.0 ng/ml for in-hospital mortality (74.3%, 70.0%; AUC=0.726). The Kaplan-Meier survival curves showed a significantly poorer prognosis in the high s-HFABP group (≥22.9 ng/ml) than in other groups. CONCLUSIONS The s-HFABP level can indicate AKI on admission, and a high s-HFABP level is associated with a poorer prognosis for AHF patients.

Association between the visiting time and the clinical findings on admission in patients with acute heart failure

BACKGROUND There have been few reports about the clinical significance of the time of admission for acute heart failure (AHF). METHODS Five hundred thirty-one patients with AHF admitted to the intensive care unit (ICU) were analyzed. The patients were assigned to either the daytime HF group (n=195, visited from 08:00 to 20:00, Group D) or nighttime HF group (n=336, visited from 20:00 to 08:00, Group N). The clinical findings and outcomes were compared between these groups. RESULTS The systolic blood pressure (SBP), the number of patients with clinical scenario (CS) 1, and the heart rate (HR) were significantly higher in group N (SBP, 171.0±38.9mmHg; CS 1, 80.9%; HR, 116.9±28.0beats/min) than in group D (SBP, 154.2±37.1mmHg; CS 1, 66.2%; HR, 108.6±31.4beats/min). The patients in group N were more likely to have orthopnea (91.1%) than those in group D (70.3%). A multivariate logistic regression model identified a SBP ≥164mmHg [odds ratio (OR): 2.043; 95% confidence interval (CI): 1.383-3.109], HR ≥114beats/min (OR: 1.490; 95%CI: 1.001-2.218), and orthopnea (OR: 2.257; 95%CI: 1.377-3.701) to be independently associated with Group N. The length of ICU stay was shorter in group N (5.8±10.5 days) than in group D (7.8±11.5 days). CONCLUSION The nighttime HF was characterized by high SBP, high HR, and orthopnea, and the length of ICU stay was shorter in the nighttime HF group.

The prognostic impact of gender in patients with acute heart failure - An evaluation of the age of female patients with severely decompensated acute heart failure.

BACKGROUND The gender differences in the prognosis of Asian patients with acute heart failure (AHF) remain to be elucidated. METHODS AND RESULTS One thousand fifty AHF patients were enrolled. The patients were assigned to a female group (n=354) and a male group (n=696). A Kaplan-Meier curve showed that the cardiovascular survival rate of the female group was significantly lower than that of the male group (p=0.005). A multivariate Cox regression model identified female gender [hazard ratio (HR): 1.381, 95% CI: 1.018-1.872] as an independent predictor of 730-day cardiovascular death. In subgroup analysis by age, in patients over 79 years, female gender significantly increased the cardiovascular death (HR: 1.715, 95% CI: 1.088-2.074, p<0.001) with a significant interaction (p-value for interaction<0.001). The prognosis, including cardiovascular death, was significantly poorer among elderly female patients (≥79 years) than among elderly male patients (p=0.019). The multivariate Cox regression model identified female gender as an independent predictor of 730-day cardiovascular death in patients who were older than 79 years of age (HR, 1.943; 95% CI, 1.192-3.167). CONCLUSIONS Female gender was associated with poor prognosis in AHF patients. In particular, old age (≥79 years) was associated with adverse outcomes in female patients with AHF.

Complete response of a patient with advanced gastric cancer, showing Epstein-Barr virus infection, to preoperative chemotherapy with S-1 and cisplatin

Here we report the case of a patient with advanced gastric cancer with esophageal invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP) preoperatively. The patient was a 72-year-old woman who was diagnosed with advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally administered at 80 mg/day (60 mg/m2 per day) on days 1–14 and CDDP was infused at 80 mg/day (60 mg/m2 per day) on day 8, followed by a 1-week rest. Marked reductions in the sizes of the primary tumor and metastatic lymph nodes around the stomach were observed after two cycles of the therapy. Adverse reactions occurring during the therapy were only grade 2 gastrointestinal disorder and grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery showed that a partial response (PR) had been achieved. The patient underwent curative surgery consisting of total gastrectomy, D2 lymph node dissection, and splenectomy. Her postoperative course was uneventful, without surgical complications. No gastric cancer cells were detected in the primary lesion or lymph nodes by immunohistochemical staining with cytokeratin, confirming a histological complete response (CR). As Epstein-Barr virus-encoded small RNA (EBER) had been detected by in-situ hybridization in the gastric cancer cells of a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and cisplatin chemotherapy.

Features and Outcomes of Patients with Calcified Nodules at Culprit Lesions of Acute Coronary Syndrome: An Optical Coherence Tomography Study

Objectives: We sought to clarify clinical features and outcomes related to calcified nodules (CN) compared with plaque rupture (PR) and plaque erosion (PE) detected by optical coherence tomography (OCT) at the culprit lesions in patients with acute coronary syndrome (ACS). Methods: Based on OCT findings for culprit lesion plaque morphologies, ACS patients with analyzable OCT images (n = 362) were classified as CN, PR, PE, and other. Results: The prevalence of CN, PR, and PE was 6% (n = 21), 45% (n = 163), and 41% (n = 149), respectively. Patients with CN were older (median 71 vs. 65 years, p = 0.03) and more diabetic (71 vs. 35%, p = 0.002) than those without CN. In OCT findings, the distal reference lumen cross-sectional area (median 4.2 vs. 5.2 mm2, p = 0.048) and the postintervention minimum lumen cross-sectional area (median 4.5 vs. 5.3 mm2, p = 0.04) were smaller in lesions with CN than in those without. Kaplan-Meier estimate survival curves showed that the 500-day survival without target lesion revascularization (TLR) was lower (p = 0.011) for patients with CN (72.9%) than for those with PR (89.3%) or PE (94.8%). Conclusions: ACS patients with CN at the culprit lesion had more TLR compared to those with PR or PE.

Matrix Metalloproteinase-9 as a Marker for Plaque Rupture and a Predictor of Adverse Clinical Outcome in Patients with Acute Coronary Syndrome: An Optical Coherence Tomography Study

Objectives: The present study sought to clarify the relationship between matrix metalloproteinase-9 (MMP-9) levels and plaque morphology demonstrated by optical coherence tomography (OCT), and to examine their prognostic impacts in patients with acute coronary syndrome (ACS). Methods: MMP-9 levels were measured for patients with ACS (n = 249). Among 249 patients, 120 with evaluable OCT images were categorized into patients with ruptured plaques (n = 65) and those with nonruptured plaques (n = 55) on the basis of culprit lesion plaque morphology demonstrated by OCT. Results: MMP-9 levels on admission were significantly higher in the rupture group than in the nonrupture group (p = 0.029). Although creatine kinase-MB (CK-MB) on admission was comparable between the groups, peak CK-MB was higher in the rupture group than in the nonrupture group (p < 0.001). By receiver operating characteristic curve analysis, the optimal cut-off value of MMP-9 to detect ruptured plaques was 65.5 ng/ml (p = 0.029). There was a nonstatistically significant trend toward increased cardiac death at 2 years (5.9 vs. 1.0%, p = 0.059) in patients with high MMP-9 (≥65.5 ng/ml) compared to those with low MMP-9 (<65.5 ng/ml). Conclusions: MMP-9 can differentiate ACS with ruptured plaques from nonruptured plaques, and MMP-9 may be a valuable predictor of long-term cardiac mortality in patients with ACS reflecting plaque rupture.

Social determinants are crucial factors in the long-term prognosis of severely decompensated acute heart failure in patients over 75 years of age

BACKGROUND The association between social factors and the long-term prognosis of acute heart failure (AHF) remains unclear. METHODS AND RESULTS One thousand fifty-one AHF patients were screened, and 915 were enrolled. Four hundred forty-two AHF patients ≥75 years of age (the elderly cohort) were also included in a sub-analysis. Participants who fulfilled one of the three marital status-, offspring-, and living status-related criteria were considered socially vulnerable. On this basis they were classified into the socially vulnerable (n=396) and non-socially vulnerable (n=519) groups in the overall cohort, and the socially vulnerable (n=219) and non-socially vulnerable (n=223) groups in the elderly cohort. Kaplan-Meier curves showed that the survival rate of the socially vulnerable group was significantly poorer than that of the non-socially vulnerable group in the overall (p=0.049) and elderly (p=0.004) cohorts. A multivariate Cox regression model revealed that social vulnerability was an independent predictor of 1000-day mortality in the overall [hazard ratio (HR): 1.340, 95% confidence interval (CI): 1.003-1.043, p=0.048] and elderly cohort (HR: 1.531, 95% CI: 1.027-2.280, p=0.036). Regarding the components of social vulnerability, the marital status was an independent factor in the elderly cohort (HR: 1.500, 95% CI 1.043-2.157, p=0.029). CONCLUSION Social vulnerability was independently associated with long-term outcomes in AHF patients, especially in the elderly cohort. Organization of the social structure of AHF patients might be able to improve their prognosis.