Luc Zyw

Risk factors and prognostic value of daytime Cheyne-Stokes respiration in chronic heart failure patients.

BACKGROUND Sleep-related Cheyne-Stokes (CS) respiration is a known phenomenon in chronic heart failure (CHF). We aimed to study the prevalence, clinical correlates, risk factors and prognostic relevance of daytime CS, as well as its relation with neurohormonal derangement. METHODS One hundred forty seven CHF patients with left ventricular systolic dysfunction (age: 64+/-12 years, ejection fraction, EF, 31+/-8%, mean+/-SD) underwent morning polygraphic recording, in addition to comprehensive clinical and neurohormonal evaluation. RESULTS Daytime CS was detected in 87 patients (59%), and associated with worse NYHA class (2.6+/-0.7 vs 2.2+/-0.8, P<0.05), lower EF (29+/-8 vs 33+/-8%, P<0.05), peak oxygen consumption (11.3+/-8.3 vs 13.4+/-4 mL/min/kg, P<0.05), resting carbon dioxide level (33.1+/-4.2 vs 37.9+/-3.8 mm Hg, P<0.001), higher norepinephrine [588 (395-939) vs (331-681) ng/L, median (interquartile range) P<0.01] and natriuretic peptides [ANP: 136 (57-230) vs 66 (18-103); BNP: 284 (99-510) vs 64 (21-202); NT-proBNP: 2575 (814-3320) vs 448 (147-1599) ng/L, all: P<0.001]. At univariate analysis, CS risk factors were age, EF, carbon dioxide, creatinine, norepinephrine, natriuretic peptides, whereas age and NT-proBNP level were the only multivariate predictors. On a 33-month follow-up, CS resulted among univariate predictors of cardiac death, NT-proBNP emerging as the only variable at multivariate analysis. CONCLUSIONS Daytime CS is frequent in CHF and is correlated with clinical severity, neurohormonal derangement, particularly of NT-proBNP, and long-term prognosis.

Prognostic Value of Plasma Renin Activity in Heart Failure

The prognostic role of specific biomarkers of the renin-angiotensin-aldosterone system and sympathetic activation pathways in heart failure has never been investigated in populations with current evidence-weighted treatment. To establish whether the plasma renin activity (PRA), among several neurohormonal biomarkers, is able to predict cardiac events in a population of patients with heart failure on up-to-date treatment, we selected 996 consecutive patients with systolic left ventricular dysfunction (ejection fraction <50%, mean age 65 ± 13 years), who underwent a complete clinical and humoral characterization and were then followed up (median 36 months, range 0 to 72) for cardiac death and appropriate implantable cardioverter device shock. We recorded 170 cardiac deaths and 27 shocks. On Cox multivariate analysis, only ejection fraction (hazard ratio 0.962, 95% confidence interval 0.938 to 0.986), N-terminal pro-brain natriuretic peptide (NT-proBNP; hazard ratio 1.729, 95% confidence interval 1.383 to 2.161) and PRA (hazard ratio 1.201, 95% confidence interval 1.024 to 1.408) were independent predictors of cardiac death. Receiver operating characteristic curve analysis identified a cutoff value for PRA of 2.30 ng/ml/hour that best predicted cardiac mortality. Independent predictors of PRA were ejection fraction, functional class, sodium, potassium, NT-proBNP, norepinephrine, aldosterone, C-reactive protein, and medical therapy. The association of high NT-proBNP and high PRA identified a subgroup (22% of the study population) with the greatest risk of cardiac death. In conclusion, PRA resulted an independent prognostic marker in patients with systolic heart failure additive to NT-proBNP level and ejection fraction. PRA might help to select those patients needing an enhanced therapeutic effort, possibly targeting incomplete renin-angiotensin-aldosterone system blockade.

Cardiovascular risk factors and gamma-glutamyltransferase fractions in healthy individuals

Abstract Background: Serum γ-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects. Methods: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects. Results: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only. Conclusions: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events. Clin Chem Lab Med 2010;48:713–7.

Prognostic Value of Combined Measurement of Brain Natriuretic Peptide and Triiodothyronine in Heart Failure

BACKGROUND Both low free triiodothyronine (fT3) and high brain natriuretic peptide (BNP) have been separately described as prognostic predictors for mortality in heart failure (HF). We investigated whether their prognostic value is independent. METHODS AND RESULTS From January of 2001 to December of 2006, we prospectively evaluated 442 consecutive patients with systolic HF and no thyroid disease or treatment with drugs affecting thyroid function (age 65+/-12 years, mean +/- standard deviation, 75% were male, left ventricular ejection fraction 33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class III and IV: 37%). All patients underwent full clinical and echocardiographic evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause mortality (cumulative) were considered as end points. During a median 36-month follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac causes. Univariate Cox model predictors of all-cause mortality and cardiac death were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class, BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class, hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and NYHA class, BNP, and fT3 as independent predictors for cardiac mortality. Patients with low fT3 and higher BNP showed the highest risk of all-cause and cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8, confidence interval, 5.4-35.2, respectively, compared with patients with normal fT3 and low BNP). CONCLUSION fT3 and BNP hold an independent and additive prognostic value in HF.

Analytical performance and clinical results of a fully automated MEIA system for brain natriuretic peptide assay: comparison with a point of care testing method

Abstract The aim of this study was to evaluate the analytical performance of a recently available immunoassay for brain natriuretic peptide (BNP), based on microparticle enzyme immunoassay (MEIA, AxSYM System, Abbott Laboratories), whose analytical characteristics and clinical results were compared with those of a point of care testing (POCT) method (TRIAGE system, Biosite Diagnostics). The within-run and total imprecision of the MEIA system were 18.4% and 19.8% at 21 ng/l, 8.0% and 14.8% at 183 ng/l, and 5.7% and 14.0% at 319 ng/l, respectively. The detection limit of the MEIA system was tested by repeatedly measuring (n = 20) the 0 calibrator in four different runs; a mean +3 SD value of 5.6 ± 4.8 ng/l (range 1.8–12.6 ng/l) was obtained. A close linear relationship (MEIA = –22.5 + 1.71 POCT method, R = 0.950, n = 296) was found (BNP concentration: 5–5500 ng/l), with a significant bias (mean difference: 164.8 ng/l, p < 0.0001). Mean BNP concentration measured in 94 reference subjects (57 women and 37 men; mean age 43.5 ± 14.0 years) was higher with MEIA than POCT, (25.9 ± 32.7 ng/l vs. 11.7 ± 8.9 ng/l, p < 0.0001). The same trend was observed also in 202 cardiac patients (620.6 ± 1082.2 ng/l vs. 386.1 ± 594.5 ng/l, p < 0.0001). Our data suggest that MEIA and POCT have quite similar analytical performance but different clinical results. Then, different reference values, as well as cut-off values, should be taken into account for the clinical use of these two immunoassays.

Prognostic value of plasma renin activity in heart failure patients with chronic kidney disease.

BACKGROUND Impairment of kidney function is frequently observed in chronic heart failure (CHF). It correlates with clinical and neurohormonal status, and affects prognosis. We aimed to identify the prognostic impact of plasma renin activity (PRA) in patients affected by CHF with chronic kidney disease (CKD). METHODS We enrolled 996 consecutive CHF patients (age 65 ± 13 years, mean ± SD, left ventricular ejection fraction, LVEF, 33 ± 10%), who underwent a complete clinical and neurohormonal characterization and were then followed-up (median 36 months) for the end point of cardiac death. RESULTS A stage ≥ 3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was found in 437 patients. Impaired renal function was associated with worse symptoms, lower LVEF, higher plasma norepinephrine, NT-proBNP and PRA (all p<0.001). As compared to patients with preserved renal function, those with CKD had higher cardiac mortality [106 (24%) vs 53 (9.5%), p<0.001]. In CKD patients, at Cox multivariate analysis, only ejection fraction (HR 0.91, 95% CI 0.84-0.97, p=0.008), NT-proBNP (2.53, 1.45-4.41, p=0.001) and PRA (1.73, 1.16-2.58, p=0.007) were independent predictors of cardiac death. ROC analysis identified a cut-off value for PRA of 3.29 ng/mL/h that predicted prognosis with the greatest accuracy. Finally, the elevation of both NT-proBNP and PRA identified a subset of patients with the highest risk of cardiac death. CONCLUSIONS PRA has an independent prognostic value in CHF patients with CKD comorbidity. The combination of PRA and NT-proBNP identifies a group of high risk patients, who might benefit of a more intensive care, targeted to enhance renin-angiotensin system antagonism.

Low triiodothyronine and exercise capacity in heart failure

BACKGROUND Cardiopulmonary exercise test (CPT) has a prominent value in assessing clinical severity in chronic heart failure (HF) patients. Reduced free triiodothyronine (fT3) plasma level is associated with a more severe disease and prognosis. The aim of this study was to evaluate the relationship between low fT3 plasma level and reduced exercise capacity in chronic HF, and to determine the influence of a low T3 status in subsets of patients with different functional impairment. METHODS AND RESULTS 240 HF patients (79% males; age 62 ± 12 years, mean ± standard deviation; left ventricular ejection fraction, EF, 30 ± 9%) underwent a CPT, clinical and neurohormonal characterization (assay for plasma brain natriuretic peptide, BNP, norepinephrine, aldosterone, renin activity, fT3, free T4, thyroid-stimulating hormone). At multivariate analysis in the whole population, age, gender and BNP level were independently associated with peak VO2, whereas in patients with severe functional impairment (peak VO2 < 14 ml/min/kg) fT3 resulted independently related to peak VO2, together with gender and BNP. When patients with peak VO2 < 14 ml/min/kg were divided according to fT3 levels, patients with low T3 syndrome showed reduced exercise capacity and worse ventilatory efficiency. CONCLUSIONS BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients.

Diagnostic accuracy of B-type natriuretic hormone for congenital heart disease in the first month of life

Abstract Background: The goal of the present study was to evaluate the diagnostic accuracy of B-type natriuretic hormone (BNP) assay in children with congenital heart disease (CHD) in the first month of life. Methods: BNP was measured in 152 neonates with CHD; 154 healthy children matched for age were used as controls. BNP was measured with a fully automated platform (Triage BNP reagents, Access Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA, USA). Results: BNP values were significantly higher (p<0.0001) in newborns and infants with CHD compared with control (CHD patients: median 1167.5 ng/L, range 25–54,447 ng/L; healthy children: median 150.5 ng/L, range 5–866 ng/L). The diagnostic accuracy of BNP was assessed using the receiver operating characteristic (ROC) analysis, taking into account the three different groups divided according to age. Group 1: all CHD patients and healthy newborns and infants as a whole (i.e., from birth to the 30th day of life); Group 2: from the 1st to 3rd day of life; Group 3: from the 4th to 30th day of life. The area under the curve (AUC) of the ROC curve for Group 3 (0.935) was significantly higher than that for Group 1 (0.843, p=0.009) and Group 2 (0.769, p=0.0003), while the AUC values of Group 1 and Group 2 were not significantly different (p=0.191). Conclusions: BNP may be considered a useful marker for screening in the integrated approach of newborns, infants and children with suspected CHD. However, the accuracy of the BNP assay varies greatly during the first month of extra-uterine life, showing the lowest diagnostic accuracy in the first 3 days after birth. After the second week of life, the biomarker becomes more accurate in ruling in CHD. Clin Chem Lab Med 2010;48:1333–8.

Clinical relevance of time course of BNP levels in neonates with congenital heart diseases

INTRODUCTION The aim of this study is to better characterize the time courses of BNP levels throughout the first days of life in larger populations of neonate and infant with or without congenital heart diseases (CHD) in order to increase the diagnostic accuracy of BNP assay in pediatric patients with CHD. MATERIALS AND METHODS BNP was measured by an automated platform (Triage BNP reagents, ACCESS Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA 92835) in 218 neonates and infants with different CHD; 222 healthy children, matched for age, served as controls. RESULTS BNP values were significantly higher (P<0.001) in the whole group of CHD patients (median 1029.8 ng/L, range 25-20,152 ng/L) than in controls (median 149.5 ng/L, range 9-866 ng/L). A different trend between BNP values and age was observed in healthy subjects and CHD patients. After an initial increase within the first 4 days of life, BNP values in CHD patients tend to stabilize to high values in the following days. On the contrary, in control subjects a peak of BNP levels was observed in the second or third day, followed by a progressive decrease. Therefore, the diagnostic accuracy of BNP assay, calculated in the samples collected in the first four days of life (AUC of ROC analysis 0.86, 95% CI 0.83-0.90) was significantly lower (P<0.0001) compared to samples collected from 5 days to 30 days of life (AUC 0.97, 95% CI 0.95-0.99). Optimal cut-off values for BNP assay, as calculated by ROC analysis, were also age-dependent (cutoff for the first 4 days of life: 363.5 ng/L; cutoff values from 5 to 30 days of life: 109.5 ng/L). CONCLUSIONS Our study demonstrates that differences in time-courses of BNP values between newborns with and without CHD throughout the first days of life clearly affect the diagnostic accuracy of BNP assay. Indeed, the diagnostic accuracy of BNP assay in discriminating between healthy newborns and CHD patients progressively increases after the 4th day of life. As a result, also cutoff values of BNP assay greatly change throughout the first days of life. However, decision values of BNP assay are strongly method-dependent, consequently clinicians should give great care to compare results obtained by different laboratories, especially when different methods are used.

NT-PROBNP PREDICTS MORTALITY IN ELDERLY AND VERY ELDERLY PATIENTS WITH CHRONIC SYSTOLIC HEART FAILURE

Heart failure (HF) prevalence among elderly will boost in the near future. NT-proBNP is a powerful diagnostic and prognostic biomarker in HF, despite its circulating concentrations are influenced by age and comorbidities (in particular renal dysfunction) which are more frequent with advanced age.