Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status ...in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification.
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which regulates neuronal differentiation and functions. Low levels of BDNF are because of psychological stress and ...potentially play a role in the pathogenesis of depression and cognition disorders. Because psychological stress and depression are associated with increased risk of heart failure (HF), the pathogenic link between HF and psychological status has attracted clinical attention. We hypothesized that plasma BDNF levels might be decreased in patients with HF and that BDNF could be a key factor associated with HF. We evaluated plasma BDNF levels in 242 patients with HF and 80 subjects without HF who are age and gender matched. Plasma BDNF levels were significantly lower in patients with HF (3,712 pg/ml 2,124 to 6,180) than those without HF (7,247 pg/ml 5,388 to 9,255, p <0.001) and lower in patients with HF with the New York Heart Association functional class III than class I (p = 0.01) and class II (p <0.001). Log BDNF levels correlated negatively with log B-type natriuretic peptide (r = −0.203, p = 0.03) in patients with HF. Of 61 acute decompensated patients with HF, plasma BDNF levels were significantly higher at discharge (4,194 pg/ml 2,356 to 6,916) compared with those at admission (2,749 pg/ml 1,380 to 4,161, p = 0.003). Multivariate logistic regression analysis identified log BDNF level as a significant correlate with the presence of HF (odds ratio 0.82; 95% confidence interval 0.76 to 0.91, p <0.001). In conclusion, plasma BDNF levels were decreased in patients with HF and associated with HF severity. BDNF could be a potentially clinically useful biomarker of HF reflecting possible cardio-neuronal linkage.
Prednisolone (PSL) therapy is the gold standard treatment in patients with cardiac sarcoidosis (CS). However, clinicians often have difficulty in deciding whether to discontinue PSL therapy in ...long-term management. Sixty-one consecutive patients with CS were divided into 2 groups based on the discontinuation of PSL during the median follow-up period of 9.9 years. PSL was discontinued in 12 patients because of improvement of clinical findings. There were no significant differences between the 2 groups in age, gender, left ventricular ejection fraction (LVEF), findings of imaging techniques, incidence of fatal arrhythmias and heart failure, and dose of PSL. After discontinuation of PSL, 5 patients had cardiac death, and discontinuation of PSL was significantly associated with higher cardiac mortality compared with continuation (p = 0.035). Although patients with discontinuation had improvement of LVEF after PSL treatment, LVEF decreased after discontinuation of PSL. Furthermore, discontinuation of PSL was associated with greater percent decrease in LVEF compared with continuation (p = 0.037) during the follow-up period. In conclusion, in the long-term management of patients with CS, discontinuation of PSL was associated with poor clinical outcomes and decreased LVEF, suggesting the importance of PSL maintenance therapy.
Abnormal liver function test results are often observed in acute decompensated heart failure (ADHF). However, the prognostic value of bilirubin fractionation has not been elucidated. The prognostic ...value of direct bilirubin (DB), in comparison with total bilirubin (TB), was examined in 556 consecutive patients with ADHF. Patients with elevated DB showed mostly similar patient characteristics including signs of elevated right-sided pressure (frequent hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated gamma-glutamyltransferase) and decreased cardiac output (cold extremities, decreased pulse pressure, and lower blood pressure) and other parameters of heart failure (HF) severity (increased plasma renin activity, decreased sodium, total cholesterol, and ejection fraction) to elevated TB; however, only patients with elevated DB showed a significant difference in the frequency of HF history and alkaline phosphatase value. Kaplan-Meier analysis showed that patients with elevated DB had a significantly higher rate of the composite end point of all-cause mortality or HF readmission (p = 0.021) compared with those with normal DB, whereas patients with elevated TB did not show a statistically significant difference compared with those with normal TB (NS). A multivariate Cox hazards model showed that DB was an independent predictor of adverse events (adjusted hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p = 0.034), whereas TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046, p = 0.27). Adding DB to existing prognostic variables resulted in higher C-statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674, respectively). In conclusion, elevated DB in ADHF was an independent prognostic predictor that was superior to TB. DB may be useful for further risk stratification in ADHF.
The echo Doppler end-diastolic pulmonary regurgitation (EDPR) gradient correlates well with catheter-derived pulmonary artery diastolic pressure. An elevated EDPR gradient is associated with worse ...clinical outcomes in patients with stable coronary artery disease. However, the prognostic significance of EDPR gradient in patients with heart failure (HF) is unclear. The aim of the present study was to investigate the prognostic impact of EDPR gradient in HF. We retrospectively examined 751 consecutive hospitalized patients with acute HF. Those with acute coronary syndrome or in-hospital death and those without accessible EDPR gradient data at discharge were excluded. Finally, 265 patients were examined and divided into 2 groups according to EDPR gradient (cutoff 9 mm Hg). Adverse events were defined as worsening HF and death. Patients with elevated EDPR gradient had higher B-type natriuretic peptide, lower age, and lower left ventricular ejection fraction at discharge than those with nonelevated EDPR gradient. During a median follow-up of 429 days, elevated EDPR gradient was independently associated with adverse events (hazard ratio 2.34, 95% CI 1.44 to 3.78, p <0.001) after adjustment for confounders. In conclusion, echo Doppler EDPR gradient might be a noninvasive predictor of clinical outcomes in hospitalized patients with HF.
Summary Background Abdominal aortic aneurysm (AAA) expansion is characterized by chronic inflammatory cell infiltration and extracellular matrix degradation. High-mobility group box 1 protein (HMGB1) ...is one of the damage-associated molecular pattern molecules derived from injured/necrotic and activated inflammatory cells. We investigated the expression of HMGB1 in human AAA and mouse experimental AAA. Then, we evaluated the effect of HMGB1 blockade on AAA formation in the mouse model. Methods and results Human AAA samples showed increased HMGB1 expression compared with normal aortic wall. In a mouse CaCl2 -induced AAA model, the expression of HMGB1 was increased compared with that in sham, and was positively correlated with matrix metalloproteinase (MMP)-2 and MMP-9 activity. We administered neutralizing anti-HMGB1 antibody (AAA/anti-H) or control antibody (AAA/C) to AAA mice subcutaneously every 3 days for 6 weeks. Treatment with neutralizing anti-HMGB1 antibody suppressed AAA formation, and attenuated elastin fragmentation. HMGB1 blockade markedly reduced the number of macrophages and MMP-2 and MMP-9 activity in aneurysmal tissue. The mRNA level of tumor necrosis factor-α and CD68 in the aorta was reduced in AAA/anti-H compared with AAA/C. Conclusions Elevation of HMGB1 level in aneurysmal tissue was observed in human AAA and mouse experimental AAA. HMGB1 blockade in a mouse AAA model reduced AAA progression, in association with reduced infiltration of macrophages and MMPs activity. These findings suggest a significant role for HMGB1 in the pathogenesis of AAA.
In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure–derived physiological ...index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated.
The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory–based environment.
In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease.
Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval CI: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113).
Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906)
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