Obesity,Brain Natriuretic Peptide Levels and Mortality in Patients Hospitalized With Heart Failure and Preserved Left Ventricular Systolic Function

BackgroundAn inverse relationship between brain natriuretic peptide (BNP) levels and body mass index (BMI) has been described for patients with left ventricular (LV) systolic dysfunction. In this study, the association of BMI, BNP levels and mortality in patients hospitalized for heart failure with preserved LV systolic function (HFpLVF) was investigated.MethodsOne hundred fifty consecutive patients (98% men) who were hospitalized with HFpLVF and had BNP levels measured on admission were analyzed. Patients were divided into categories of BMI: normal (BMI < 25 kg/m²), overweight (BMI 25–29.9 kg/m²) and obese (BMI ≥ 30 kg/m²). Relevant clinical and echocardiographic characteristics and all-cause mortality were obtained through chart review.ResultsBNP levels were significantly lower in obese (median = 227 pg/mL) and overweight (median = 396 pg/mL) patients compared with those with normal BMI (median = 608 pg/mL, P = 0.003). Higher BMI predicted BNP levels of <100 pg/mL. Compared with patients with normal BMI, overweight and obese patients had a significantly lower risk of total mortality, even after adjusting for other clinical characteristics, including log-transformed BNP levels, atrial fibrillation, the use of beta-blockers at discharge, age, hemoglobin levels and the presence of pulmonary congestion on admission. Higher BNP levels also independently predicted mortality.ConclusionsAn inverse relationship between BMI and BNP levels exists in patients hospitalized with HFpLVF. Higher BMI is associated with lower mortality, whereas higher BNP levels predict higher mortality in male patients with HFpLVF. These findings should be confirmed in a larger multicenter setting.     

Heterogeneity of the prognostic significance of B-type natriuretic peptide levels on admission in patients hospitalized for acute heart failure syndromes

BackgroundWe hypothesized that variation in baseline characteristics of patients with acute heart failure syndromes (AHFS) affects the prognostic significance of B-type natriuretic peptide (BNP) levels because of heterogeneity of this patient population. We evaluated the association of elevated BNP levels on admission with an increased risk of adverse clinical outcomes in subgroups of patients hospitalized for AHFS.MethodsThis study included patients from the acute decompensated heart failure syndromes (ATTEND) study, a multicenter prospective cohort of 4501 AHFS patients with BNP data on admission.ResultsThe geometric mean BNP level was 654.9 pg/mL (95% confidence interval: 636.1–674.2), and the optimal cut-off value for all-cause death was 1157 pg/mL. All-cause mortality after admission was significantly higher in patients with high BNP levels (> 1157 pg/mL) than in those with low BNP levels (≤ 1157 pg/mL) (median follow-up: 508 days, log-rank P < 0.001). Subgroup analyses were performed to evaluate the heterogeneity of the prognostic significance of BNP levels. The effect of high BNP levels on the risk of all-cause mortality was significantly greater in the subgroup of patients with a non-hypertensive etiology, low creatinine levels (< 1.3 mg/dL), and high sodium levels (≥ 135 mEq/L) than in those without these factors (P = 0.024, P < 0.001, and P < 0.001 for the interaction, respectively).ConclusionsThe present analysis shows that underlying etiology of heart failure (i.e., hypertensive), renal function, and sodium levels should be considered for assessing the clinical significance of elevated BNP levels on admission in relation to the risk of adverse outcome after hospitalization for AHFS.     

Utilidade do doseamento do peptídeo natriurético tipo B em doentes ambulatórios com insuficiência cardíaca com fração de ejeção preservada

IntroductionHeart failure with preserved ejection fraction (HFPEF) is a highly prevalent syndrome that is difficult to diagnose in outpatients. The measurement of B-type natriuretic peptide (BNP) may be useful in the diagnosis of HFPEF, but with a different cutoff from that used in the emergency room. The aim of this study was to identify the BNP cutoff for a diagnosis of HFPEF in outpatients.Methods and ResultsThis prospective, observational study enrolled 161 outpatients (aged 68.1 ± 11.5 years, 72% female) with suspected HFPEF. Patients underwent ECG, tissue Doppler imaging, and plasma BNP measurement, and were classified in accordance with algorithms for the diagnosis of HFPEF. HFPEF was confirmed in 49 patients, who presented higher BNP values (mean 144.4 pg/ml, median 113 pg/ml, vs. mean 27.6 pg/ml, median 16.7 pg/ml, p < 0.0001). The results showed a significant correlation between BNP levels and left atrial volume index (r=0.554, p < 0.0001), age (r = 0.452; p < 0.0001) and E/E′ ratio (r = 0.345, p < 0.0001). The area under the ROC curve for BNP to detect HFPEF was 0.92 (95% confidence interval: 0.87-0.96; p < 0.001), and 51 pg/ml was identified as the best cutoff to detect HFPEF, with sensitivity of 86%, specificity of 86% and accuracy of 86%.ConclusionsBNP levels in outpatients with HFPEF are significantly higher than in those without. A cutoff value of 51 pg/ml had the best diagnostic accuracy in outpatients.     

Safety and efficacy of adaptive servo-ventilation in patients with severe systolic heart failure

Background and purposeIt is unclear whether adaptive servo-ventilation (ASV) is safe and effective in patients with severe systolic heart failure (HF). Our aim in this study was to estimate the safety and efficacy of ASV therapy for patients with severe systolic HF.Methods and subjectsSeventy-six HF patients (age: 69 ± 12 years; 53 men), categorized as New York Heart Association (NYHA) Class II–IV, with left ventricular ejection fraction (LVEF) of <50%, received ASV therapy after optimal medical therapy to determine the safety and efficacy of ASV. Patients were divided into 2 groups based on their LVEF: group L (LVEF < 30%; n = 42) and group H (LVEF ≥ 30%; n = 34). After 6 months of ASV therapy, we compared the changes in LVEF, brain natriuretic peptide (BNP), and incidence of fatal cardiovascular events between the groups.ResultsThe groups differed significantly with respect to beta-blocker treatment before ASV therapy (p < 0.0001). After 6 months of ASV therapy, LVEF and BNP levels had improved in both groups. In group L, LVEF had improved from 24.1 ± 5.6% to 35.2 ± 10.6% (p < 0.0001) and BNP from 591 (273–993) pg/ml to 142 (39–325) pg/ml (p = 0.002). Moreover, 1-year follow-up data showed a tendency toward improvement of NYHA classification in group L (group L: 50%; group H: 29%; p = 0.07), and showed no significant difference with regard to fatal cardiovascular events between the 2 groups (group L: 11.9%; group H: 5.9%; p = 0.36).ConclusionsOur study demonstrated that ASV therapy is safe and effective for use in very severe systolic HF patients as well as in relatively mild systolic HF patients.     

Admission NT-proBNP levels,renal insufficiency and age as predictors of mortality in elderly patients hospitalized for acute dyspnea

BackgroundAssay of baseline B-type peptide (BNP and NT-proBNP) is useful for heart failure (HF) prognostication. In contrast, the prognostic value of NT-proBNP assay performed on admission of elderly subjects for acute dyspnea is uncertain. The aim of this study was to determine the vital prognostic value of NT-proBNP assay and other relevant variables available on admission in elderly patients hospitalized for acute dyspnea.Methods254 patients over 70 years of age who were initially hospitalized with acute dyspnea were prospectively studied. The log-rank test and Cox proportional-hazards regression models were used to determine the prognostic value of NT-proBNP and creatinine clearance, measured within 24 h of initial admission, as well as age, gender, vascular risk factors and other clinical variables.ResultsMean age was 81 ± 7 years, and 52% of the patients were women. During a median follow-up of 34 months, 134 patients (55%) died and 9 patients (4%) were lost to follow-up. The median survival time was 25 months, and almost half the deaths occurred during the first 6 months. In multivariate analysis the following three variables were independently associated with mortality (shown with their accompanying hazard ratios (HR)): NT-proBNP > 2856 pg/mL (median), HR = 1.6[95%CI:1.3–5.2]; creatinine clearance < 30 mL/min, HR = 1.7[95%CI:1.2–2.5]; and age > 80 years, HR = 1.7[95%CI:1.1–2.6]. The median survival time among patients with an admission NT-proBNP level of > 2856 pg/mL (median) was 14 months, compared to > 36 months in the rest of the population.ConclusionThe admission NT-proBNP level, age, and creatinine clearance are predictive of vital outcome in elderly patients hospitalized for acute dyspnea.     

Comparison of the ACC/AHA and Framingham algorithms to assess cardiovascular risk in HIV-infected patients

The aim of this study was to compare the predictions of Framingham cardiovascular (CV) risk score (FRS) and the American College of Cardiology/American Heart Association (ACC/AHA) risk score in an HIV outpatient clinic in the city of Vitoria, Espirito Santo, Brazil. In a cross-sectional study 341 HIV infected patients over 40 years old consecutively recruited were interviewed. Cohen's kappa coefficient was used to assess agreement between the two algorithms. 61.3% were stratified as low risk by Framingham score, compared with 54% by ACC/AHA score (Spearman correlation 0.845; p < 0.000). Only 26.1% were classified as cardiovascular high risk by Framingham compared to 46% by ACC/AHA score (Kappa = 0.745; p < 0.039). Only one out of eight patients had cardiovascular high risk by Framingham at the time of a myocardial infarction event registered up to five years before the study period. Both cardiovascular risk scores but especially Framingham underestimated high-risk patients in this HIV-infected population.     

Efficacy and safety of a 60-week treatment with candesartan in Japanese patients with mild to moderate chronic heart failure

BackgroundChronic heart failure (CHF) is an increasingly common cardiovascular disease despite recent advances in its diagnosis and management.Methods and resultsA multicenter, open-label study was designed to assess the efficacy and safety of 60-week treatment with candesartan in Japanese patients with mild to moderate CHF. Primary efficacy endpoints were changes from baseline in plasma brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), end-diastolic dimension, and New York Heart Association (NYHA) functional class. Two hundred and eighty-nine eligible patients were divided into 2 groups based on the daily dose at the end of treatment: high-dose (HD, 8 mg, N = 170) and low-dose (LD, 2 or 4 mg, N = 119). Neither plasma BNP levels nor LVEF changed from the baseline to the end of treatment in the LD group, whereas BNP significantly improved from 61.6 to 50.1 pg/mL (p = 0.0005) and LVEF from 57.2 to 60.1% (p = 0.0005) in the HD group. The changes in NYHA functional class were comparable between groups: 21.2% improved and 76.3% unchanged in the LD group and 20.6% improved and 79.4% unchanged in the HD group. No safety concerns were observed in either group.ConclusionsHD candesartan was more effective in improving plasma BNP levels and cardiac function than LD in Japanese CHF patients. Both LD and HD candesartan were well tolerated in CHF patients.     

Interacción cardiorrenal y evolución de la insuficiencia cardiaca. ¿Tiene un papel la proteína de unión del factor de crecimiento de tipo insulina 2?

Introduction and objectivesPreliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.MethodsHF patients (n = 686, mean age 66.6 years, 32.7% women) were enrolled and followed up for a median of 3.5 (min-max range: 0.1-6) years. Patients were classified as having CKD with decreased estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m²) or as having CKD with nondecreased eGFR (≥ 60 mL/min/1.73 m²). Serum IGFBP2 was detected by ELISA.ResultsIGFBP2 was increased (P < .001) in CKD patients with decreased eGFR (n = 290, 42.3%) compared with patients with nondecreased eGFR. IGFBP2 was directly associated with NT-proBNP (P < .001) and inversely associated with eGFR (P < .001), with both associations being independent of confounding factors. IGFBP2 was directly and independently associated with cardiovascular and all-cause death (P < .001) in the whole group of patients, but showed a stronger association with cardiovascular death in CKD patients with decreased eGFR (P for interaction < .05), improving risk prediction in these patients over clinically relevant risk factors.ConclusionsSerum IGFBP2 is associated with impaired renal function and prognosticates cardiovascular death in patients with HF and CKD with decreased eGFR. Thus, there is an effect modification of CKD on circulating IGFBP2 and on its association with cardiovascular mortality in HF patients.     

Relationship between BNP level and renal function in diabetic nephropathy with microalbuminuria

AimsWe examined the relationship between the brain natriuretic peptide (BNP) level and renal function in diabetic nephropathy with microalbuminuria.MethodsThe subjects were 97 Japanese type 2 diabetes mellitus outpatients with microalbuminuria. Associations between the annual rate of decline in estimated glomerular filtration rate (eGFR) and various metabolic parameters at baseline (BMI, systolic blood pressure, HbA1c, LDL cholesterol, urine albumin–creatinine ratio, BNP and eGFR) were examined.ResultsAmong the baseline factors, eGFR and BNP had significant associations with the annual rate of decline in eGFR in Pearson correlation analysis (r = 0.295, p = 0.003; r = 0.223, p = 0.028, respectively). Multiple linear regression analysis also showed the significance of baseline eGFR and BNP as independent predictors of renal function (β = 0.340, p = 0.001; β = 0.278, p = 0.005, respectively). In multivariate logistic regression analysis, eGFR and BNP were independently associated with the risk of a decline in GFR (p = 0.003, p = 0.011, respectively). ROC curve analysis showed a cutoff value of BNP is 17.0 pg/mL for predicting a decline in GFR.ConclusionsThe BNP level at baseline is an independent predictor of the annual rate of decline in eGFR. Therefore, monitoring of BNP can play an important role in management of diabetic nephropathy.     

The importance of admission and discharge BNP assessment in patients hospitalized for acutely decompensated chronic systolic heart failure

IntroductionThe assessment of B-type natriuretic peptide (BNP) plasma levels is not only useful for the differential diagnosis of acute dyspnea, but also for the prognostic stratification of patients with heart failure. However, available studies that have addressed monitoring of hospitalized patients are burdened with significant limitations: (1) measurement of plasma BNP levels only at admission or at discharge, (2) lack of details regarding the cause of heart failure, and (3) small sample size. Therefore, we conducted a prospective study of all patients presenting to our hospital with acutely decompensated chronic systolic heart failure.AimTo determine the importance of admission and discharge values of BNP and its changes during hospitalization for identification of patients with acutely decompensated chronic systolic heart failure at higher risk of unfavorable course of the disease.MethodsA prospective monocentric study determining plasma BNP levels at admission and at discharge in patients hospitalized for acutely decompensated chronic systolic heart failure. Patients: 130 consecutive patients, 77% men, mean age 70 years, body mass index (BMI) 27.8 kg/m²; etiology of chronic heart failure—65.9% ischemic heart disease, 29.5% dilated cardiomyopathy, 4.6% others; signs and symptoms at admission—peripheral edema 58.9%, pulmonary rates 88.3%, orthopnea 53.1%, median of admission BNP 1101 pg/ml, median of discharge BNP 650 pg/ml, median left ventricular ejection fraction 26.5%, average length of hospitalization 9 days.ResultsDuring the follow-up (mean 15 months) the total mortality rate reached almost 40% and the annual mortality of our cohort was 29%. The most common causes of death included progression of heart failure and acute coronary syndromes. To evaluate the long-term risk of mortality, we used time-dependent ROC curves for the definition of cut-off values of BNP at admission and discharge. The relationship of BNP levels and the survival of patients was assessed using the hazard ratio (HR) calculated by the Cox proportional hazards model. BNPs at admission and at discharge with a cut-off value of 1699 pg/ml and 434.5 pg/ml are significant prognostic factors for patients hospitalized for acutely decompensated chronic systolic heart failure with a HR 2.79 and 3.29, respectively. During the follow-up, more than half of the patients required readmission to the hospital. The most common reasons for rehospitalization were cardiovascular causes.ConclusionBNP levels at admission and at discharge are an important predictive factor of survival in patients with acutely decompensated chronic systolic heart failure.     

Potential use of Brain Natriuretic Peptide in patients with asymptomatic significant mitral stenosis

ObjectiveTo evaluate the ability of BNP to identify a subset of patients with asymptomatic significant rheumatic MS, who get symptoms on stress exercise testing.MethodsSeventy asymptomatic patients with significant rheumatic MS (MVA ⩽1.5 cm²) were included in the study. All patients underwent resting echo-Doppler study, exercise echocardiography and BNP level assessment pre- and one week post-balloon dilatation (for group I patients who had PMC).Patients were divided into two groups. Group I included 33 patients who became symptomatic on exercise and had low exercise capacity. Group II included 37 patients who were asymptomatic on exercise and had reasonable exercise capacity.ResultsBNP level in group I was 92 ± 12 compared to 40 ± 10 pg/ml in group II, P < 0.001. Post PMC, BNP in group I significantly decreased (92 ± 12, compared to 31 ± 9 pg/dl, P < 0.001). LA dimension was significantly different between both groups (50 ± 2.9 in group I compared to 46 ± 3.1 mm in group II, P < 0.001). Post-exercise SPAP was 72 ± 12 in group I compared to 46 ± 13 mmHg in group II, P < 0.001. Post-exercise MV gradient was 28 ± 9 compared to 20 ± 12 mmHg, P = 0.002. BNP significantly correlated with post-exercise SPAP (r = 0.635; P < 0.001). Area under the ROC curve for BNP as a predictor of low exercise capacity and development of symptoms on exercise was 0.98 [CI 95% 0.96–1.0]. When using a cutoff value of 55 pg/mL for BNP, sensitivity was 93.9% and specificity was 91.9%.ConclusionBNP may be used to approach asymptomatic patients with significant MS. BNP may identify a subset of patients with exercise-induced clinical and echo-Doppler criteria that meet the contemporary guidelines for intervention.     

The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: The Multi-Ethnic Study of Atherosclerosis

ObjectiveUnder physiological conditions brain natriuretic peptide (BNP) is inversely associated with metabolic risk factors, but under pathological conditions these associations may tend to plateau.Material and methods5597 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA), 45–84 years of age, free of overt cardiovascular disease in 2000–02 and then again in 2003–05 participated in this study. Associations between NT-proBNP and BMI, blood lipids, homeostasis model of insulin resistance (HOMA-IR) using linear regression models were adjusted for age, race, sex, BMI, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes and glomerular filtration rate. The inflection points (IP) at which these associations became nonlinear were determined using linear splines with knots at different levels of NT-proBNP.ResultsParticipants with NT-proBNP ≥ 100 pg/mL (29%) tended to be older, on statins and anti-hypertensive medications vs. those with NT-proBNP < 100 pg/mL. The IP point varies among variables and ranged from 50–120 pg/mL. NT-proBNP < IP, associated inversely with BMI, total cholesterol (TC), LDL-C, triglycerides (TG) and HOMA-IR, but positively with HDL-C. A higher proportion of participants with NT-proBNP ≥ 100 pg/mL had subclinical CVD. All associations with NT-proBNP plateaued when NT-proBNP ≥ IP. Baseline level in NT-proBNP was not associated with 3-year change in BMI, TG, HDL-C or fasting glucose.ConclusionsIn a large cardiovascular disease-free cohort, NT-proBNP within the lower (physiological) range was inversely associated with TC, LDL-C, TG and insulin resistance with different inflection points, but at higher (pathological) levels these associations were blunted.     

Vascular access and angiographic lesion morphology in elective percutaneous coronary intervention

Many coronary interventionists have a perception that the radial route may not facilitate complex PCI. This study evaluates the association between target lesion morphology, vessel characteristics and angiographic outcome in elective PCI cases carried out through radial versus femoral artery approach.MethodsElective PCI cases over a 23 month period at a tertiary care hospital were reviewed for this analysis. Modified ACC/AHA classification was used to ascertain the impact of different arterial accesses in elective PCI on the angiographic outcome with the complex angiographic lesion morphologies.Results343 Patients and 407 lesions were analyzed. Radial access was the final route in 253 procedures treating a total of 300 lesions, while femoral access was the final route in 90 PCI procedures for treating 107 lesions. Lesion complexity incidence in radial PCI group by using modified ACC/AHA classifications A, B1, B2, and C were 4.67%, 15%, 60.33% and 20%, respectively. While in the femoral PCI, the incidence of lesion types was 6.54%, 15.89%, 42.99%, and 34.58%, respectively. By summation of the complex end of the spectrum for ACC/AHA lesion types B2 plus C, the incidence was 241 lesions (80.33%) in radial PCI vs. 83 lesions (77.57%) in femoral PCI, P = 0.25. Angiographic successful outcome according to the combined end point was achieved in 283 lesions (94.33%) for radial PCI vs. 92 lesions (85.99%) in femoral PCI, P = 0.004.ConclusionThis study confirms that a default radial PCI is an effective strategy for the majority of complex lesions in elective PCI.     

Association of adiponectin with peripheral muscle status in elderly patients with heart failure

BackgroundReduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.MethodsWe measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.ResultsSerum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.ConclusionsOur findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.     

Micro RNA-146a expression,NF-κB/P65 activity and serum pentosidine levels as potential biomarkers for disease severity in primary knee osteoarthritis patients

IntroductionIdentifying osteoarthritis (OA) patients at high risk for progression is important.Aim of the workTo study the expression pattern of micro RNA-146a (miR-146a), NF-κB/p65 binding activity and serum pentosidine levels in patients with primary knee OA (KOA) in order to assess their value as potential markers for disease prognosis and severity and to clarify their role in disease pathogenesis.Patient and methodsThis study was conducted on 36 female patients with primary KOA divided radiologically into those with moderate KOA and severe KOA as well as 20 controls. The expression patterns of miR-146a were analyzed using quantitative real time-PCR, NF-κB/p65 binding activity and serum pentosidine levels determined using ELISA kits.ResultsmiR-146a expression levels were significantly higher in KOA patients than controls being significantly higher in moderate KOA compared to severe cases. NF-κB/p65 binding activity and serum pentosidine levels were significantly higher in severe KOA patients (0.74 ± 0.06 and 425.2 ± 40.3 pg/ml) compared to moderate cases (0.3 ± 0.03 and 311.4 ± 30 pg/ml) (p < 0.05) and were higher compared to controls (0.15 ± 0.08 and 257 ± 32.3 pg/ml respectively) (p < 0.05).ConclusionThis study may emphasize the role of miR-146a expression, and NFKB/p65 binding activity in primary KOA. Assessment of NFKB/p65 binding activity, miR-146a expression, and serum pentosidine in primary KOA patients could extend the panel of laboratory tests available to monitor the severity and progress of the disease and might benefit as markers for detection of patients with high risk for disease progression; and hence to be a novel therapeutic target to inhibit cartilage destruction.     

Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure

Background and purposeHyponatremia is common and is associated with poor in-hospital outcomes in patients hospitalized with heart failure (HF). However, it is unknown whether hyponatremia is associated with long-term adverse outcomes. The purpose of this study was to clarify the characteristics, clinical status on admission, and management during hospitalization according to the serum sodium concentration on admission, and determine whether hyponatremia was associated with in-hospital as well as long-term outcomes in 1677 patients hospitalized with worsening HF on index hospitalization registered in the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD).Methods and subjectsWe studied the characteristics and in-hospital treatment in 1659 patients hospitalized with worsening HF by using the JCARE-CARD database. Patients were divided into 2 groups according to serum sodium concentration on admission <135 mEq/mL (n = 176; 10.6%) or ≥135 mEq/mL (n = 1483; 89.4%).ResultsThe mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and mean left ventricular ejection fraction was 42.4%. After adjustment for covariates, hyponatremia was independently associated with in-hospital death [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265–4.755, p = 0.008]. It was significantly associated also with adverse long-term (mean 2.1 ± 0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433–2.657), cardiac death (OR 2.053, 95% CI 1.413–2.983), and rehospitalization due to worsening HF (OR 1.488, 95% CI 1.134–1.953).ConclusionsHyponatremia was independently associated with not only in-hospital but also long-term adverse outcomes in patients hospitalized with worsening HF.     

Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure

BackgroundThe origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity.MethodsLPS responsiveness was studied in 122 patients with chronic HF (mean ± SD: age 67.3 ± 10.3 years, 24 female, New York Heart Association class [NYHA] class: 2.5 ± 0.8, left ventricular ejection fraction [LVEF]: 33.5 ± 12.5%) and 27 control subjects of similar age (63.7 ± 7.7 years, p > 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver–operator characteristic curve (ROC) analysis.ResultsA total of 56 patients with chronic HF died from any cause during follow-up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0–16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2–61.4%) and specificity of 81.5% (95% confidence interval 61.9–93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01–0.67, p < 0.05).ConclusionsLPS responsiveness in patients with chronic HF is an independent predictor of death.     

An integrated multiple marker modality is superior to NT-proBNP alone in prognostic prediction in all-cause mortality in a prospective cohort of elderly heart failure patients

BackgroundIdentifying the individual mortality risk for elderly heart failure (HF) patients is challenging because of heterogeneity, comorbidity and higher age. To overcome this, an integrated multiple marker modality has been proposed for better prognostic prediction than a single variable, this has not been evaluated.AimThe aim of this study is to identify whether a multiple marker modality is better than N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone for all-cause mortality in elderly HF patients.MethodsA prospective cohort of 361 patients (65 ± 15 years) referred for echocardiography because of suspected HF was studied, among them, 179 had HF (71 ± 13). In this cohort blood sampling, electrocardiogram and clinical examinations were performed within approximately 24 hours after the echocardiography. To assess prognostic value of multiple marker modality for all-cause mortality, patients were followed up for 24 ± 7 months.ResultsIn the three multivariate analyses, NT-proBNP, cystatin C, red blood cell distribution width (RDW), midregional pro-atrial natriuretic peptide (MR-proANP), pulmonary artery pressure, estimated glomerular filtration rate (eGFR) less than 60 mL/min, anemia, diuretics and sinus rhythm are prognostic predictors of all-cause mortality in elderly HF patients. When analyzing all these variables in one multivariate analysis, only NT-proBNP, eGFR less than 60 mL/min, anemia and diuretics are prognostic predictors of all-cause mortality in elderly HF patients. Two different multiple marker models incorporating NT-proBNP, clinical and laboratory variables were created. The sensitivity and specificity of the two different multiple marker modalities are higher than for NT-proBNP alone. The risk score based on multivariate analysis Wald X² values is preferred considering its simplicity and feasibility in daily clinical practice.ConclusionA multiple marker modality was proven to improve prognostic prediction in elderly HF patients compared to NT-proBNP alone.     

Punto de corte óptimo del antígeno carbohidrato 125 para la identificación de pacientes con bajo riesgo tras un ingreso por insuficiencia cardiaca aguda

Introduction and objectivesCarbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF.MethodsThe derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n = 1583).ResultsIn the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was < 23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 < 23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%CI, 0.08-0.50; P < .001), and the combined endpoint (HR, 0.63; 95%CI, 950.45-0.90; P = .009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up.ConclusionsIn patients admitted with AHF, CA125 < 23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring.Full English text available from:www.revespcardiol.org/en