Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-Atrial Fibrillation Trial
JOURNAL OF INTERNAL MEDICINE
Authors: Latini, R.; Masson, S.; Pirelli, S.; Barlera, S.; Pulitano, G.; Carbonieri, E.; Gulizia, M.; Vago, T.; Favero, C.; Zdunek, D.; Struck, J.; Staszewsky, L.; Maggioni, A. P.; Franzosi, M. G.; Disertori, M.
Abstract
Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M on the behalf of the GISSI-AF Investigators (Istituto di Ricerche Farmacologiche "Mario Negri", Milan; Istituti Ospitalieri, Cremona; POL Madonna della Consolazione, Reggio Calabria; Ospedale Nuovo Girolimo Fracastoro, San Bonifacio; Ospedale Garibaldi-Nesima, Catania; Ospedale Luigi Sacco, Milan, Italy; Roche Diagnostics, Rotkreuz, Switzerland; B.R.A.H.M.S. AG, Henningsdorf, Germany; ANMCO Research Center, Florence; and Ospedale Santa Chiara, Trento, Italy). Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-Atrial Fibrillation Trial. J Intern Med 2011; 269: 160-171. Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). Background. Predicting long-term maintenance of sinus rhythm in patients with AF is difficult. Methods. Plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. Results. Mean patient age was 68 +/- 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.
The Combination of Biomarkers for Prognostication of Long-Term Outcome in Patients Treated with Mild Hypothermia After Out-of-Hospital Cardiac Arrest-A Pilot Study
THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT
Authors: Annborn, Martin; Nilsson, Fredrik; Dankiewicz, Josef; Rundgren, Malin; Hertel, Sabine; Struck, Joachim; Cronberg, Tobias; Nielsen, Niklas
Abstract
To explore if the brain biomarker neuron-specific enolase (NSE) in combination with a biomarker for stress; CT-proAVP (copeptin), oxidation; peroxiredoxin 4 (Prx4), inflammation; procalcitonin (PCT), or with biomarkers from the heart; midregional proatrial natriuretic peptide (MR-proANP), or troponin T (TnT) can improve the prognostic accuracy of long-term outcome after out-of-hospital cardiac arrest (OHCA). Serum samples from cardiac arrest patients, treated at 33 degrees C for 24 hours, were collected serially at 12, 24, and 48 hours after cardiac arrest. The concentration of the investigated biomarkers was measured using stored samples, and long-term outcome was evaluated by the cerebral performance category (CPC) at 6 months. Poor outcome was defined as CPC 3-5. Sixty-two patients with OHCA of presumed cardiac cause were included. NSE had best prognostic accuracy for poor outcome at 48 hours with a receiver operating characteristic area under curve (AUC) of 0.94 (95% confidence interval [CI] 0.87-1). The combination of NSE with TnT, both at 48 hours, increased the AUC to 0.98 (95% CI 0.95-1, likelihood ratio [LR] test p-value 0.07, net reclassification index [NRI] <0.001); NSE and MR-proANP, both at 12 hours, yielded an AUC of 0.91 (95% CI 0.80-1, LR test p-value 0.0014, NRI p-value 0.003); NSE at 48 hours with MR-proANP at 12 hours yielded an AUC of 0.97 (95% CI 0.92-1, LR test p-value 0.055, NRI p-value 0.04). This pilot study suggests that a combination of biomarkers with NSE could be beneficial for improving early prognostication of long-term outcome following OHCA.