Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction.

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014-1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.

Prognostic value of cardiovascular magnetic resonance imaging for life-threatening arrhythmia detected by implantable cardioverter-defibrillator in Japanese patients with hypertrophic cardiomyopathy.

Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death in HCM patients. We reviewed ICD records to analyze the relation between life-threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients. In 102 consecutive patients (median age 63 years, 63 males) implanted with an ICD after CMR with gadolinium enhancement (median follow-up 2.8 years), the outcome of life-threatening arrhythmic events (appropriate ICD interventions for ventricular tachycardia or ventricular fibrillation) was examined. Appropriate interventions rate were 10.3% per year for secondary prevention and 7.4% per year for primary prevention. The annualized ICD-related complication rate was 3.7%. 43/91 patients (47%) implanted ICD for primary prevention had maximum wall thickness ≥20 mm plus LGE in ≥4 of 17 left ventricular segments (cut-off value obtained from ROC curve); the appropriate ICD intervention rate was significantly higher in this group than in other patients group (annualized event rate, 11.1 vs. 4.6%; log-rank P = 0.038). A combination of myocardial hypertrophy and LGE is a useful outcome predictive factor for life-threatening ventricular arrhythmia in Japanese HCM patients.

Effect of Obesity on the Prognostic Impact of Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although obesity is associated with left ventricular hypertrophy, diastolic dysfunction, and occurrence of atrial fibrillation (AF), obese heart failure (HF) patients have a more favorable clinical outcome (obesity paradox). The clinical impact of AF on obese or lean HF patients has not been fully elucidated.Methods and Results:We analyzed 1,681 patients who were enrolled in the West Tokyo Heart Failure Registry (WET-HF Registry), a multicenter, prospective cohort registry from 2005 through 2014. We assigned them to 3 categories based on body mass index (BMI): low, BMI <18.5; medium, BMI ≥18.5 and <25; and high, BMI ≥25 (n=182/915/400). The clinical endpoint was all-cause death or readmission for acute decompensated HF. During 406 days of follow-up (IQR, 116-739 days), AF was associated with a higher risk of the endpoint in the HF with preserved ejection fraction (HFpEF) group (P<0.001, log-rank test), but not in the HF with reduced EF (HFrEF) group. AF was associated with a higher risk of the endpoint in low and medium BMI patients with HFpEF (P=0.016 and 0.009, respectively). On Multivariate Cox proportional hazards analysis, AF was an independent predictor of the endpoint in patients with BMI <25 from the HFpEF group (hazard ratio, 1.74; 95% CI: 1.21-2.54, P=0.003), but not in the other subgroups. CONCLUSIONS: AF had a negative impact on clinical outcome in non-obese patients with HFpEF.

Validation of the Get With The Guideline-Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level.

BACKGROUND: Detailed characteristics of patients with acute heart failure (AHF) in Japan have not been elucidated. Furthermore, international application of risk models obtained in the United States has not been validated. METHODS: We evaluated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score performance in AHF patients enrolled in the West Tokyo Heart Failure registry, a large, ongoing, prospective, multicenter cohort registry. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, blood urea nitrogen level, sodium concentration, and presence of chronic obstructive pulmonary disease. Score discrimination and calibration were evaluated by the c statistic, Hosmer-Lemeshow statistic, and visual plotting. We conducted additional analyses to determine whether other variables improved the performance of the score. The primary outcome was in-hospital mortality. RESULTS: In total, 1,876 patients were admitted for AHF between April 2006 and August 2014. The patients were predominantly men (60.6%), with a mean age of 73.3 ± 13.6 years. Sixty-eight (3.6%) patients died during hospitalization. The GWTG-HF risk score showed acceptable discrimination; the c statistic for in-hospital mortality in this cohort was 0.763 (95% CI, 0.700-0.826). The calibration plot showed good conformance between the predicted and observed in-hospital mortality. Notably, addition of B-type natriuretic peptide level to the conventional GWTG-HF score significantly improved the discrimination (c statistic, 0.818; 95% CI, 0.771-0.865). CONCLUSIONS: The GWTG-HF risk score can be applied in Japanese AHF patients with good discrimination and calibration. Furthermore, addition of B-type natriuretic peptide level improves discrimination and could be considered in future risk models.

Correlation of Pre- and In-Hospital Systolic Blood Pressure in Acute Heart Failure Patients and the Prognostic Implications　- Report From the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

BACKGROUND: Systolic blood pressure (SBP) is an important prognostic indicator for patients with acute heart failure (AHF). However, its changes and the effects in the different phases of the acute management process are not well known.Methods and Results:The Tokyo CCU Network prospectively collects on-site information about AHF from emergency medical services (EMS) and the emergency room (ER). The association between in-hospital death and SBP at 2 different time points (on-site SBP [measured by EMS] and in-hospital SBP [measured at the ER; ER-SBP]) was analyzed. From 2010 to 2012, a total of 5,669 patients were registered and stratified into groups according to both their on-site SBP and ER-SBP: >160 mmHg; 100-160 mmHg; and <100 mmHg. In-hospital mortality rates increased when both on-site SBP and ER-SBP were low. After multivariate adjustment, both SBPs were inversely associated with in-hospital death. Notably, the risk for patients with ER-SBP of 100-160 mmHg (intermediate risk) differed according to their on-site SBP; those with on-site SBP <100 or 100-160 mmHg were at higher risk (OR, 7.39; 95% CI, 4.00-13.6 and OR, 2.73; 95% CI, 1.83-4.08, respectively [P<0.001 for both]) than patients with on-site SBP >160 mmHg. CONCLUSIONS: Monitoring changes in SBP assisted risk stratification of AHF patients, particularly patients with intermediate ER-SBP measurements. (Circ J 2016; 80: 2473-2481).

Impact of Triggering Events on Outcomes of Acute Heart Failure.

BACKGROUND: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. METHODS: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. RESULTS: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P = .0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. CONCLUSION: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

Incidence of hospital-acquired hyponatremia by the dose and type of diuretics among patients with acute heart failure and its association with long-term outcomes.

BACKGROUND: Diuretics are the cornerstone therapy for acute heart failure (AHF) but can lead to various electrolyte disturbances and inversely affect the patients' outcome. We aimed to evaluate whether (1) the dose of loop diuretics could predict hospital-acquired hyponatremia (HAH) during AHF treatment, (2) addition of thiazide diuretics could affect development of HAH, and (3) assess their impact on long-term outcomes. METHODS: We analyzed the subjects enrolled in the multicenter AHF registry (WET-HF). Risk of HAH, defined as hyponatremia at discharge with normonatremia upon admission, was evaluated based on oral non-potassium-sparing diuretics via multivariate logistic regression analysis. Additionally, we performed one-to-one matched analysis based on propensity scores for thiazide diuretics use and compared long-term mortality. RESULTS: Of total 1163 patients (mean age 72.6±13.6 years, male 62.6%), 92 (7.9%) had HAH. Compared with low-dose loop diuretics users (<40mg; without thiazide diuretics), risks for developing HAH were significantly higher in patients with thiazide diuretics, regardless of the dose of loop diuretics (OR 2.67, 95% CI 1.13-6.34 and OR 2.31, 95% CI 1.50-5.13 for low- and high-dose loop diuretics, respectively). The association was less apparent in patients without thiazide diuretics (OR 1.29, 95% CI 0.73-2.27 for high-dose loop diuretics alone). Among 206 matched patients, all-cause and cardiac mortality rate was 27% and 14% in non thiazide diuretics users and 50% and 30% in thiazide diuretics users, respectively (HR 2.46, 95% CI 1.29-4.69, p=0.006 and HR 2.50, 95% CI 1.10-5.67, p=0.028, respectively) during a mean 19.3 months of follow-up. CONCLUSIONS: Thiazide diuretics use, rather than loop diuretics dose, was independently associated with HAH; and mortality was higher in thiazide diuretics users even after statistical matching.

Effect of Heart Failure Secondary to Ischemic Cardiomyopathy on Body Weight and Blood Pressure.

Both the obesity paradox and blood pressure (BP) paradox remain ill defined. Because both obesity and hypertension are well-known predictors of coronary artery disease (CAD) and acute heart failure (HF), in the present study, we compared the obesity paradox and the BP paradox between patients with acute HF with and without a history of CAD. A multicenter retrospective study was conducted on 3,204 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; multivariate Cox regression analysis with backward stepwise selection was then used to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 27% of patients had a history of CAD, and the all-cause in-hospital mortality rate was 5%. In-hospital mortality was significantly lower for patients with obesity than in those without obesity (log-rank, p = 0.033). However, this obesity paradox disappeared in the group with HF and CAD (log-rank, p = 0.740). In contrast, in-hospital mortality was significantly lower for patients with high BP at admission, regardless of the presence of a history of CAD (log-rank, p <0.001 for both groups). In conclusion, a history of CAD canceled the obesity paradox in patients with acute HF, whereas the BP paradox persisted regardless of a history of CAD.

A CD14 gene polymorphism is associated with the IgE level for Dermatophagoides pteronyssinus.

CONCLUSION: CD14/-159 plays a role in sensitization to Dermatophagoides pteronyssinus in Japanese patients with allergic rhinitis. OBJECTIVE: An association between a polymorphism in the 5'-flanking region of the CD14 gene and atopic phenotypes has been identified in a pediatric American population and an adult Dutch population. The aim of this study was to determine whether the CD14/-159 polymorphism is associated with specific IgE levels in allergic rhinitis patients in a Japanese population. MATERIAL AND METHODS: The CD14/-159 genotypes of 81 unrelated patients with allergic rhinitis and 78 healthy subjects were determined and compared. The total IgE level and the specific IgE levels for three aeroallergens were determined. The IgE levels for each genotype were compared. RESULTS: The frequencies of CD14/-159 genotypes did not differ between the two groups. Among the allergic rhinitis patients, TT homozygotes had significantly fewer positive CAP-radioallergosorbent tests (CAP-RASTs) than CC homozygotes and CT heterozygotes, suggesting that the C allele is dominant. TT homozygotes also had significantly lower CAP-RAST scores for Dermatophagoides pteronyssinus, but not for Cryptomeria japonica or Dactylis glomerata, than CC homozygotes and CT heterozygotes. There was no significant association between total serum IgE levels and CD14/-159 genotypes in the allergic rhinitis patients.

Effect of estimated plasma volume reduction on renal function for acute heart failure differs between patients with preserved and reduced ejection fraction.

BACKGROUND: The prognostic relevance of plasma volume reduction (PVR) in acute heart failure patients remains unclear because of the confounding hemodynamic effect of left ventricular ejection fraction impairment on kidney function. METHODS AND RESULTS: Subjects enrolled in the West Tokyo Heart Failure Registry were examined. The PV at admission and discharge was estimated from the subjects' body weight and its deviation from the ideal body weight. Patients in the top tertile of estimated PVR were classified as PVR+. Of the 381 patients with acute heart failure, 181 (47.5%) had heart failure with preserved ejection fraction (HFpEF). Estimated PVR was associated with worsening renal function in the HFpEF (odds ratio, 3.28; 95% confidence interval, 1.55-6.96; P=0.002) but not in the heart failure with reduced ejection fraction cohort (odds ratio, 1.22; 95% confidence interval, 0.61-2.42; P=0.57). This association in the HFpEF cohort remained significant after adjusting for a history of hypertension and diabetes mellitus and the estimated glomerular filtration rate (odds ratio, 3.34; 95% confidence interval, 1.52-7.33; P=0.003). The use of intravenous diuretics was a significant predictor of PVR in the HFpEF and heart failure with reduced ejection fraction groups. CONCLUSIONS: The effect of estimated PVR differs by HF type, and the estimated PVR during hospitalization is a predictor of worsening renal function in patients with HFpEF but not in heart failure with reduced ejection fraction. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.html. Unique identifier: UMIN000001549.

Effects of dexamethasone on mucin gene expression in cultured human nasal epithelial cells.

OBJECTIVE: To clarify 1) which mucin gene expression is influenced by glucocorticoid and 2) whether glucocorticoid influences steady-state mucin expression or mucin gene expression induced by lipopolysaccharide. METHODS: Dissociated cells obtained from nasal polyps were cultured on a collagen gel substrate in an air-liquid interface. Dexamethasone was added to the culture medium in the steady-state and prior to the stimulation by LPS. RNAs were extracted from culture cells, and semiquantitative reverse transcriptase-polymerase chain reaction was performed for MUC2, MUC5AC, MUC5B, MUC8, and beta-actin. RESULTS: Dexamethasone did not influence steady-state messenger RNA levels of either mucin gene. Dexamethasone suppressed lipopolysaccharide-induced messenger RNA levels of MUC8. CONCLUSION: Glucocorticoid does not influence steady-state mucin gene expression but suppresses mucin gene expression induced by secretagogues such as lipopolysaccharide.

Mucin gene expression in the effusions of otitis media with effusion.

OBJECTIVES: The purpose of the study is to know if mucin gene expression can be detected in the middle ear effusion and if so, which mucin genes are expressed in the effusions. METHODS: Mucin gene expression in the middle ear effusions obtained from five patients with otitis media with effusion were analyzed by reverse transcription-polymerase chain reaction. Ribonucleic acids (RNAs) were extracted from the effusion and the expression of 12 mucin genes was analyzed by reverse transcription-polymerase chain reaction. RESULTS: Mucin gene expression examined by reverse transcription-polymerase chain reaction indicated the expression of MUC1, MUC4, MUC5AC, MUC6, MUC7, MUC8, MUC9, MUC11 and MUC12 mRNA in the effusion. This mucin gene expression was similar to that in BEAS-2B cell, a bronchial epithelial cell line. CONCLUSION: Middle ear effusion can give us valuable information on mucin gene expression in the middle ear. There is similarity between mucin gene expression in the middle ear effusion and that in the bronchial epithelia.