172 pg/ml) (p < 0,001) mit höheren Werten von NT-proB- ... 1390 pg/ml) and without (1093 vs. ..... tide concentrations in dyspneic subjects with and without.
original article
Wien Klin Wochenschr (2009) 121: 700–706 DOI 10.1007/s00508-009-1269-5 Printed in Austria © Springer-Verlag 2009
Wiener klinische Wochenschrift The Middle European Journal of Medicine
Atrial fibrillation is an independent determinant of increased NT-proBNP levels in outpatients with signs and symptoms of heart failure Borut Jug1, Miran Šebeštjen1, Mišo Šabovicˇ1, Maja Pohar 2, Irena Keber1 1 Department 2 Institute
of Vascular Diseases, Division of Internal Medicine, University Clinical Center, Ljubljana, Slovenia of Bioinformatics and Biostatistics, School of Medicine, University of Ljubljana, Ljubljana, Slovenia
Received February 8, 2009, accepted after revision September 7, 2009
Vorhofflimmern ist eine unabhängige Determinante erhöhter NT-proBNP Werte bei Patienten mit Herzinsuffizienz Zusammenfassung. Hintergrund und Fragestellung: Das N-terminale pro-B-Typ natriuretische Peptid (NT-proBNP) wird zunehmend sowohl in der Diagnostik als auch bei der prognostischen Einschätzung von Herzinsuffizienz verwendet. Allerdings ist der Einfluss des Vorhofflimmerns auf die NT-proBNP-Werte noch unklar. Deshalb haben wir den Einfluss von Vorhofflimmern auf die NT-proBNP Werte bei Patienten mit Herz insuffizienzsymptomatik analysiert. Patienten und Methodik: Zufällig ausgewählte Patienten (n = 306), die in die Ambulanz für Herzinsuffizienz der Universitätsklinik Ljubljana aufgrund von Symp tome und klinischen Zeichen einer Herzinsuffizienz eingewiesen wurden, wurden klinisch und elektrokardiographisch untersucht. Außerdem wurde bei jedem Patienten das NT-proBNP bestimmt (durch Einsatz einer „Sandwich chemiluminescent immunoassay“ Methode mit zwei Antikörpern auf dem Elecsys Analysator). Ergebnisse: Vorhofflimmern war sowohl bei den Patienten mit (mediane Konzentration 1944 vs. 1390 pg/ mL) als auch ohne strukturelle Herzkrankheit (1093 vs. 172 pg/ml) (p 7 days prior to assessment. Patients with previous documented episodes of paroxysmal atrial fibrillation were included in the sinus rhythm group if they were in sinus rhythm at the time of analysis. As part of routine clinical care all patients underwent echocardiographic assessment with M-mode and two-dimensional echocardiography and Doppler ultrasound. Systolic dysfunction was defined by an ejection fraction 120 beats/minute), as well as patients with newly diagnosed atrial fibrillation and duration of symptoms 2 groups) for normally distributed variables, a Mann-Whitney U-test (Kruskal-Wallis with Bonferroni modification in > 2 groups) for asymmetrically distributed variables, or the chi-squared test for categorical variables. Receiver operating curves (ROCs) were constructed to determine the diagnostic utility of NT-proBNP levels for prediction of the presence of structural heart disease in patients with sinus rhythm and in patients with atrial fibrillation; results are expressed in terms of area under the curve (AUC) and 95% CI for this area. Optimal cut-off values were obtained from the respective ROC curve using the highest combined sensitivity and specificity. Graphic representation was used to explore the interrelationship between left ventricular ejection fraction (LVEF) and NT-proBNP levels in patients with sinus rhythm and in patients with atrial fibrillation. The influence of atrial fibrillation on NT-proBNP levels was then assessed using a non-parsimonious linear regression model with propensity score adjustments [11] to balance for possible confounders known to affect NT-proBNP levels and significantly different between patients with and without atrial fibrillation. Propensity scores were derived from predicted probabilities in logistic-regression models with atrial fibrillaAtrial fibrillation and NT-proBNP
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original article
tion as an outcome. Multiple imputation was used to allow for missing variables when calculating the propensity score. Patients were then matched using the nearest available Mahalanobis metric matching (based on main covariates) with callipers defined by the propensity score. A linear regression model was fitted on this smaller but balanced sample. A P value ≤ 0.05 was considered statistically significant. The statistical package R 2.2.0 for Windows was used for calculations.
Results A total of 306 patients were included in the study. The median age was 73.6 years (interquartile range 64.0– 79.2), 156 (51%) patients were female. Overall, 225 (73.5%) patients had echocardiographic evidence of cardiac dysfunction and 102 (33.3%) had atrial fibrillation (80 patients with underlying structural heart disease, 22 patients without). Structural heart disease was primarily characterized by left ventricular systolic dysfunction in 139 (62%) patients, isolated left ventricular diastolic dysfunction in 72 (32%), primary valvular disease in 9 (4%), other (i.e. right ventricular dysfunction or severe left ventricular hypertrophy) in 5 (2%). Regarding etiology, 88 (39%) of the 225 patients with structural heart disease had ischemic heart disease, 61 (27%) had hypertensive heart disease, 36 (16%) had combined ischemic and hypertensive heart disease, 22 (10%) had idiopathic dilatational cardiomyopathy, 9 (4%) had organic valvular disease and 9 (4%) had other or unclassified heart disease. In the 81 patients without structural heart disease, symptoms were attributed to pulmonary disease in 28 (34%) patients, physical deconditioning in 45 (56%), anemia in 5 (6%) and other or miscellaneous causes in 3 (4%). Patients with atrial fibrillation without underlying structural heart disease had significantly higher median levels of NT-proBNP than patients without cardiac dysfunction in sinus rhythm; patients with secondary atrial fibrillation (i.e. atrial fibrillation with underlying structural heart disease) had significantly higher median levels of NT-proBNP than controls with structural heart disease in sinus rhythm (Fig. 1). We also confirmed a strong association between NT-proBNP levels and LVEF in both sinus rhythm (r = –0.510; P
