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(Circulation. 2007;116:I-1 – I-7.)
© 2007 American Heart Association, Inc.

Arrhythmia Surgery

Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass

Mias Pretorius, MBChB, MSc; Brian S. Donahue, MD, PhD; Chang Yu, PhD; James P. Greelish, MD; Dan M. Roden, MD; Nancy J. Brown, MD

From the Departments of Anesthesiology (M.P., B.S.D.), Biostatistics (C.Y.), and Cardiac Surgery (J.P.G.), and the Division of Clinical Pharmacology (M.P., D.M.R., N.J.B.) Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, Tenn.

Correspondence to Mias Pretorius, MBChB, MSc, 560 RRB, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail mias.pretorius{at}vanderbilt.edu

Background— Postoperative atrial fibrillation (AF), leading to significant morbidity and prolongation of hospital stay, complicates 20% to 40% of surgical procedures requiring cardiopulmonary bypass (CPB). This study tests the hypothesis that biomarkers predict the development of postoperative AF.

Methods and Results— We enrolled 253 adult patients undergoing elective cardiac surgery requiring CPB and who were in sinus rhythm at the time of surgery. Blood samples were obtained for measurement of 21 biomarkers immediately after separation from CPB and administration of protamine. Patients who developed postoperative AF (67 subjects, 26.5%) were significantly older (P<0.001), more likely to have a remote history of AF (P<0.001), and tended to be more likely to have had valve surgery (P=0.082). Plasminogen activator inhibitor-1 (P=0.014), interleukin (IL)-6 (P=0.019), and N-terminal prohormone brain natriuretic peptide (P=0.028) concentrations were significantly higher in the blood of patients who developed postoperative AF. Logistic regression identified age (P<0.001), remote history of AF (P=0.001), and postoperative PAI-1 (P=0.036) as independent predictors of postoperative AF. When preoperative PAI-1 antigen concentrations were included in the model age (P<0.001), remote history of AF (P<0.001) and preoperative PAI-1 (P=0.015) were identified as independent predictors of postoperative AF. The Chi-squared Automatic Interaction Detection (CHAID) model indicated that age was the primary determinant for the development of postoperative AF (17% in age 67.3 years versus 49% in age >67.3 years). Within younger patients (age 67.3 years) without remote history of AF, postoperative PAI-1 antigen concentration next determined risk of AF (13% if PAI-128.5 ng/mL versus 46% if PAI-1>28.5 ng/mL).

Conclusion— An elevated preoperative or postoperative PAI-1 antigen concentration is an independent predictor for development of AF after CPB. Studies are needed to determine whether drugs that reduce PAI-1 concentrations can also reduce the risk of postoperative AF.

Key Words: atrial fibrillation • plasminogen activator inhibitor • inflammation • cardiopulmonary bypass