C. Prontera

Proficiency testing project for brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) immunoassays: the CardioOrmocheck study.

Abstract Background: We organized and conducted a proficiency testing study (CardioOrmocheck) to evaluate the differences in analytical performance of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) immunoassays. Methods: Approximately 90 Italian laboratories were involved in the 2005–2007 proficiency testing cycles, while 112 laboratories took part in the 2008 cycle (from January to May 2008). A total of 28 study samples were measured by participating laboratories for a total of 2354 determinations. Results: The mean total variability for BNP (50.6 %CV) was significantly higher than that for NT-proBNP (8.4 %CV). In addition, the mean variability due to differences between-methods (46.4 %CV) comprised the majority of the total variability for BNP. Between-method variability for BNP comprised, on average, 84% of total variability, while the within-method variability comprised an average of 20.2 %CV. On the contrary, for NT-proBNP the within-method variability (7.3 %CV) represented the majority of total variability (average 75%), while between-method variability was smaller (4.1 %CV). Imprecision around the cut-off value showed marked differences among methods, especially for BNP immunoassay methods. In addition, BNP methods were affected by large systematic differences, for example an average 2.7-fold difference between Access and ADVIA Centaur methods, while agreement between NT-proBNP methods was better (an average 1.2-fold difference between Dimension and ECLIA on the Elecsys methods). Conclusions: This multicenter collaborative study demonstrates that there are significant differences in analytical characteristics and measured values among the most popular commercial methods for BNP and NT-proBNP. Clinicians should be very careful when comparing results obtained by laboratories that use different methods. Clin Chem Lab Med 2009;47:762–8.

Neuro-hormonal activation predicts ventilatory response to exercise and functional capacity in patients with heart failure.

Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro‐hormonal activation is a hallmark of HF and influences its clinical evolution.

Increased levels of C-type natriuretic peptide in patients with idiopathic left ventricular dysfunction

C-type natriuretic peptide (CNP) is expressed in the vascular endothelium. It is not known whether CNP is specifically increased in patients with idiopathic left ventricular systolic dysfunction (ILVDys) with or without overt heart failure, and whether in these patients it is related with indicators of myocardial and/or endothelial/microvascular impairment. We determined plasma CNP levels in 51 ILVDys and in 60 controls. We observed a significant increase in patients with (7.0+/-0.9 pg/ml) or without (6.1+/-0.53 pg/ml) overt heart failure (p<0.001) in respect to controls (2.5+/-0.12 pg/ml). CNP was significantly correlated with LVEF (p<0.001), end-diastolic dimension (p<0.05), ANP (p<0.001) and BNP (p<0.001), interleukin-6 (p<0.001), total cholesterol (p<0.05), low-density lipoprotein (p=0.05), ratio total cholesterol/ high-density lipoprotein (p=0.05) and, in a subgroup of patients, with abnormal vasodilating capacity of the coronary microcirculation. In conclusion, CNP is activated in patients with LV dysfunction but without coronary artery disease, independently of the presence of overt heart failure and in tune with the extent of myocardial functional involvement. In these patients CNP is also related with both systemic and coronary indicators of endothelial/microvascular damage.

Amino-Terminal Fragment of Pro-Brain Natriuretic Hormone Identifies Functional Impairment and Right Ventricular Overload in Operated Tetralogy of Fallot Patients

To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), functional capacity, and right ventricular overload in survivors of tetralogy of Fallot (TOF) repair, we prospectively studied 70 operated TOF patients (44 males, 21xa0±xa01 years old; meanxa0±xa0SEM) who underwent, during the same day, echocardiography, cardiac magnetic resonance imaging, neurohormonal characterization (plasma NT-proBNP, catecholamines, plasma renin activity, and aldosterone assay), and cardiopulmonary exercise testing. Forty-eight age- and sex-matched healthy volunteers served as the control group. Compared to controls, maximal workload and peak oxygen consumption (VO2/kg) were lower in operated TOF patients (pxa0<xa00.001), whereas NT-proBNP concentration was elevated (pxa0<xa00.001). No difference was found among the other neurohormones. In operated TOF patients, NT-proBNP showed a significant positive correlation with right ventricular (RV) end systolic and end diastolic volumes and RV systolic pressure, and it showed a negative correlation with peak VO2/kg and RV ejection fraction. From multivariable analysis, NT-proBNP concentration was found to be an independent predictor of peak VO2/kg, RV end systolic volume, and RV systolic pressure. These results show an association among RV overload, decrease in functional capacity, and cardiac natriuretic peptide expression in operated TOF patients. NT-proBNP plasma assay may be a useful tool for diagnostic purposes and for decision making in this setting.

71 Improved early diagnosis of heart failure with B‐type natriuretic peptides: comparison between BNP and NT‐proBNP diagnostic accuracy

Background: There is speculation that natriuretic peptides may be “falsely elevated” in patients with renal dysfunction. These patients could have higher BNP levels due to higher filling pressures caused by renal dysfunction or due to decreased renal filtration and clearance by renal endopeptidases. Methods: We analyzed 111 patients who underwent cardiac catheterization. eGFR was calculated using mod. MDRD equation. The population was stratified by PCWP (15mm Hg) to include congested patients. Patients were then subclassified using K/DOQI Classification of Renal Function into stage II mild(eGFR 60-90), stage III moderate(eGFR 3060) and stage IV severe(eGFR 15-30) renal dysfunction while excluding dialysis patients. BNP was measured using Biosite® Assay. AUC, linear regression, and t student test were performed. Results: LogBNP was useful in distinguishing patients with CHF from patients without CHF (AUC=73%, 95%CI, 60% to 87%, p<0.001) in patients with eGFR between 30-90 ml/min/1.73m2; mean BNP was 1143pg/ml in the CHF group vs. 531pg/ml in no CHF (p=0.003). However, logBNP could not distinguish CHF patients from patients without CHF in the groupwith eGFR between 15-29ml/min/1.73m2 (AUC=52%, 95%CI, 6% to 98%, p=0.68).

The clinical diagnosis of heart failure is predicted by neurohormonal and immune derangement

Abstract To characterize the complex picture of neurohormonal abnormalities in heart failure (HF), a comprehensive characterization was prospectively performed in 105xa0patients with cardiomyopathy at different clinical stages and compared to 47xa0sex/age-matched control healthy subjects. To assess the relationship between the diagnosis of HF and clinical and neurohumoral variables, multiple logistic regression with forward stepwise selection (Wald) was used. The diseased condition was predicted by creatinine level, gamma-glutamyl transpeptidase (GGT) activity, TNF-alpha, and plasma levels of several neurohormonal indices: (a) plasma renin activity; angiotensin II; aldosterone; (b) cortisol as a stress marker; (c) norepinephrine levels; (d) triiodothyronine; (e) ANP and BNP. Thus, renal and hepatic dysfunction, overexpression of cardiac natriuretic hormones, of adrenergic and renin–angiotensin–aldosterone system significantly augment the probability of HF, which was decreased by increasing values of thyroid hormone. In conclusion, a complex neurohormonal derangement associated with an overall predominance of vasoconstrictor systems is characteristic of HF syndrome.