Atsutoshi Takagi

Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome

BACKGROUND Recently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated. METHODS AND RESULTS This study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24 h after percutaneous coronary intervention. RESULTS U-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019). CONCLUSIONS These data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS.

Estimated glomerular filtration rate is an independent predictor for mortality of patients with acute heart failure.

BACKGROUND Heart failure is a major public health problem in developed countries including Japan, therefore it is important to estimate the future risk in patients with heart failure. Recently, it has been reported that chronic kidney disease (CKD) is an independent predictor for mortality in chronic heart failure. However, it is unknown whether CKD is an independent predictor for mortality in acute heart failure. We retrospectively investigated the relationship between estimated glomerular filtration rate (eGFR) on admission for acute heart failure and long-term mortality. METHODS We analyzed 194 patients who were admitted for acute heart failure from January, 2002 to February, 2005. Patients were divided into two groups, high-eGFR group (eGFR <60 ml/min, n=75) and low-eGFR group (eGFR > or =60 ml/min, n=119). eGFR was calculated by equation of MDRD (modification of the diet in renal disease) study. eGFR level <60 ml/min/1.73 m(2) is impaired renal function according to the guidelines of the Japanese Society of Nephrology and of the National Kidney Foundation. Serum B-type natriuretic peptide (BNP) level and left ventricular ejection fraction (LVEF), anemia, age, gender, and etiology of heart failure were also evaluated. Median observation period was 609 days (range: 30-1627). Mean age was 69 years and 138 patients were male. RESULTS Median eGFR on admission was 74.2 ml/min (range: 5.48-238.7), median BNP level was 840 pg/ml (range: 200-4800), and median LVEF was 36% (range: 11-81%). Forty-two percent of patients had eGFR <60 ml/min of eGFR at the time of coronary care unit admission. Patients with low-eGFR had a significantly lower mortality rate by Kaplan-Meier analysis (log rank test, p=0.013). By Coxs proportional-hazard analysis, eGFR was an independent factor for long-term mortality of acute heart failure (p=0.039). CONCLUSIONS Lower eGFR at the time of admission could be an independent predictor for mortality of acute heart failure.

Association between elevated blood glucose level on admission and long-term mortality in patients with acute decompensated heart failure

BACKGROUND The effect of elevated blood glucose (BG) levels on the long-term prognosis of acute decompensated heart failure (ADHF) patients has not been well defined. The purpose of this study is to evaluate the long-term prognosis of ADHF with elevated BG. METHODS A cohort of patients consecutively admitted to the cardiac intensive care unit from 2007 to 2011 was studied. Among these, 495 patients who met the criteria were divided into 4 groups based on their BG level and diabetes mellitus (DM) status. The risks for all-cause mortality in each group were assessed using the multivariate Cox proportional hazards model. RESULTS At a median follow-up of 1.8 years, 148 patients had died. There were 168 patients without either BG elevation or DM, 67 without BG elevation but with DM, 105 with BG elevation but not DM, and 155 with both BG elevation and DM. In a multivariate model, those with BG elevation, regardless of DM status, showed a greater risk of increased mortality when compared with patients without either BG elevation or DM [hazard ratio (HR), 1.79; p=0.042 for BG elevation without DM and HR, 1.73; p=0.048 for BG elevation with DM]. CONCLUSION Elevated BG levels, irrespective of the DM status, at the time of admission in patients with ADHF, appear to be a prognostic marker for ADHF.

Red cell distribution width predicts short- and long-term outcomes of acute congestive heart failure more effectively than hemoglobin

The present study compared short- and long-term prognostic values of red blood cell distribution width (RDW) with those of hemoglobin (Hgb) among patients with acute congestive heart failure (CHF) in a cardiac care unit. The cross-sectional study examined data from 521 patients with acute CHF who were admitted to a cardiac care unit and followed up for 24 months (median). Mean Hgb levels in patients who succumbed (DIH) or remained alive (AIH) were 11.0±1.8 and 11.8±2.6 g/l (P>0.05), respectively. Median values of RDW were 16.2% and 14.4%, respectively (P<0.0001). During the 24-month follow-up, mean levels of Hgb in groups with and without endpoints were 11.4±2.5 and 12.5±2.4 g/dl (P<0.0001), respectively. Median RDW values were 14.9 and 13.8%, respectively (P<0.0001). Logistic regression analysis showed that in-hospital mortality was significantly associated with RDW (P=0.044), New York Heart Association (NYHA) functional class IV (P=0.0037), estimated glomerular filtration rate (eGFR) (P=0.042) and C-reactive protein (P=0.0044), but not with Hgb (P=0.10). The multivariate Cox proportional hazard model selected RDW [hazard ratio (HR), 2.19; P<0.0001], left ventricular ejection fraction (HR 0.81, P=0.0016), age (10-year increase; HR 1.19, P=0.0017) and NYHA functional classes III/IV (HR 1.52, P=0.0029) as independent predictors of long-term outcomes after adjustment, but not Hgb (HR 1.01, P=0.86). Higher RDW values in acute CHF patients at admission were associated with worse short- and long-term outcomes and RDW values were more prognostically relevant than Hgb levels.

Prevalence of amiodarone-induced thyrotoxicosis and associated risk factors in Japanese patients.

Amiodarone is a widely used agent for life-threatening arrhythmias. Although amiodarone-induced thyrotoxicosis (AIT) is a major adverse effect that can cause recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT among amiodarone-treated Japanese patients have not been elucidated. Here, we investigated the prevalence and predictive factors for AIT. The study subjects were 225 patients treated with amiodarone between 2008 and 2012, who were euthyroid before amiodarone therapy. All patients with AIT were diagnosed by measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13 patients (5.8%) developed AIT and all the patients were classified as Type 2 AIT. Baseline features of patients with AIT were not different from those who did not develop AIT, except for age (AIT, 55.1 ± 13.8, non-AIT, 68.1 ± 12.0 years, P < 0.001). Multivariate analyses using the Cox proportional hazard model identified age as the sole determinant of AIT (hazard ratio: 0.927, 95% confidence interval: 0.891–0.964). Receiver operating characteristic curve analysis identified age of 63.5 years as the cutoff value for AIT with sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and that young age is a risk factor for AIT.

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database

Aims There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear. Methods The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality. Results The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51−0.99; P = 0.043). Conclusions Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients.

Ischemic Cardiomyopathy with a Rapid Progression from Thrombotic Thrombocytopenic Purpura.

An 83-year-old woman who complained of dizziness and nausea visited our hospital. An electrocardiogram showed ST-segment elevation in multiple leads and an echocardiogram showed severe hypokinesis of the anteroseptal wall of the left ventricle. However, emergency coronary angiography showed no stenotic lesions in any coronary arteries. A laboratory examination showed thrombocytopenia, renal dysfunction, and hemolysis. We therefore diagnosed the patient with thrombotic thrombocytopenic purpura (TTP). While we were preparing to initiate plasma exchange therapy, she suddenly developed cardiopulmonary arrest. A postmortem examination revealed microthrombi in the small vessels of the myocardium. We herein report a case of ischemic cardiomyopathy with a rapid progression from TTP.

Significance of Serum Polyunsaturated Fatty Acid Level Imbalance in Patients with Acute Venous Thromboembolism

Aim: Polyunsaturated fatty acids (PUFAs) take part in various biological events linked to the pathogenesis of venous thromboembolism (VTE), including inflammation, endothelial dysfunction, and hypercoagulability. Several studies have demonstrated the association between PUFAs and the occurrence of VTE. However, the role of PUFAs in the pathogenesis of VTE remains unclear. Methods: We enrolled 45 patients with acute VTE and 37 age-, gender-, and body mass indexmatched healthy volunteers to examine their PUFA levels. Serum omega 3 (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) and omega 6 (dihomogammalinolenic acid: DGLA and arachidonic acid: AA) fatty acids levels were measured within 24 h of admission. Results: Patients with VTE showed significantly higher AA and lower EPA levels, and lower EPA/AA ratios than the controls. Multivariate analysis revealed that AA was an independent marker for VTE. In addition, we divided the patients based on their median age (58 years old). The younger patients with VTE showed significantly lower EPA/AA levels than their age-matched controls, whereas older patients with VTE showed a significantly higher AA/DGLA levels than the older controls. Conclusions: High serum AA levels and low EPA levels are associated with the development of acute VTE, suggesting that the imbalance of PUFAs may be a potential therapeutic target for preventing acute VTE.

In‑hospital and long‑term outcomes of congestive heart failure: Predictive value of B‑type and amino‑terminal pro‑B‑type natriuretic peptides and their ratio

Relative changes in B-type natriuretic peptide (BNP) and amino terminal pro-BNP (NT-proBNP) levels may help to assess the risk of congestive heart failure (CHF). However, whether these levels at the time of admission enable the prediction of outcomes with acute exacerbation remains unknown. The current study determined the abilities of BNP, NT-proBNP and their ratio to predict in-hospital and long-term outcomes of patients with CHF. Patients who were admitted to the cardiac care unit of Juntendo University Hospital (Tokyo, Japan) with acute CHF onset were consecutively enrolled into the present observational study. Serum levels of BNP and NT-proBNP were immediately measured on admission, and other biomarkers and clinical data were also investigated. Of 195 enrolled patients, 16 (8.2%) succumbed to CHF in hospital and 124 (69.3%) reached the endpoint of mortality or readmission following a median follow-up of 14 months. Multiple linear regression analysis revealed body mass index, low density lipoprotein cholesterol, hemoglobin, estimated glomerular filtration rate and C-reactive protein as independent predictors of the NT-proBNP/BNP ratio. BNP, NT-proBNP and their ratio were significantly higher among those who succumbed to CHF than in those who remained alive in hospital (P<0.05). Logistic regression analysis indicated that the ratio was an independent predictor for in-hospital mortality and long-term outcomes. In conclusion, the ratio of NT-proBNP to BNP more effectively predicts in-hospital outcomes than either factor alone and it may also help to predict outcomes among patients with acute exacerbation of HF.

Rapidly progressed aortic stenosis in a patient with previous diagnosis of polycythemia vera and post‐polycythemia vera myelofibrosis

Polycythemia vera (PV) is a chronic myeloproliferative disease that is often complicated with thromboembolism. However, aortic stenosis (AS) could be a manifestation of the cardiovascular complications of PV possibly through shear stress and atherosclerosis. We report a rare case of rapidly progressed AS in a patient with PV.