Letter Regarding Article by Mandal et al, “Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation”
To the Editor:
Mandal and colleagues1 report a novel association between anti–heat shock protein (HSP) 65 antibodies and the occurrence of postoperative atrial fibrillation (AF), indicating a possible role for antibody-mediated immune response in its pathogenesis.
The authors report significant associations between postoperative AF and anti-HSP65 antibodies, a history of previous myocardial infarction, duration of cardiopulmonary bypass, number of distal anastomoses, and duration of ventilation by univariate analysis. In addition, lower levels of anti-HSP65 antibodies and grafting the left anterior descending artery seemed to be independently associated with a decreased occurrence of postoperative AF by multivariate analysis. The present study did not, however, find an association between age, preoperative and postoperative use of β-adrenergic blockers, and postoperative AF.
Increasing age has been a consistent independent predictor for AF after cardiac surgical procedures in most previous trials and meta-analyses.2–5 In addition, previous studies and reviews2 consistently found that preoperative β-blocking agents protect against postoperative AF.
Because the present study is in contrast with previous data on the association between age, preoperative β-blockade, and postoperative AF, the study population may not reflect a representative sample of patients undergoing coronary artery bypass surgery, which might limit possible clinical implications of the present findings.
Mandal K, Jahangiri M, Mulhin M, Poloniecki J, Camm AJ, Xu Q. Association of anti-heat shock protein 65 antibodies with development of postoperative atrial fibrillation. Circulation. 2004; 110: 2588–2590.
Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation. 2002; 106: 75–80.
Aranki SF, Shaw DP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M, Collins JJ Jr, Cohn LH, Burstin HR. Predictors of atrial fibrillation after coronary artery surgery: current trends and impact on hospital resources. Circulation. 1996; 94: 390–397.
Auer J, Weber T, Berent R, Puschmann R, Hartl P, Ng CK, Schwarz C, Lehner E, Strasser U, Lassnig E, Lamm G, Eber B; Study of Prevention of Postoperative Atrial Fibrillation. A comparison between oral antarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the Pilot Study of Prevention of Postoperative Atrial Fibrillation (SPPAF), a randomized placebo-controlled trial. Am Heart J. 2004; 147: 636–643.
Auer J, Weber T, Berent R, et al. Risk factors of postoperative atrial fibrillation after cardiac surgery. J Cardiac Surg. In press.
We thank Dr Auer and colleagues for their interest in our article.1 We agree that β-blocker use has been associated with postoperative AF in many of the previous trials and studies. From the point of view of associated pathophysiology, it is acute withdrawal of β-blockers in the postoperative period that makes these patients more prone to postoperative AF. In recognition of this knowledge, we had decided to have all of the patients in our study take atenolol 25 mg OD on day 1 postoperatively. This is clearly mentioned in the methodology section, under the subheading “Postoperative AF.” Given the fact that all of our patients were taking β-blockers postoperatively, we obviously could not have demonstrated this as one of the risk factors for development of postoperative AF in our study.
We also agree with Auer and colleagues that age is another important predictor associated with postoperative AF; however, evidence against its importance also exists in the literature.2,3 In our study (see Table 1 in the original article), patients with postoperative AF also were older than those without AF (65±7 years versus 64±9 years; P=0.14). The failure to identify, as predictors of postoperative AF, some variables that have been linked with this arrhythmia in other series can be an expression of the reduced statistical power. The fact that, despite the reduced power, we were able to clearly define a relationship between HSP65 antibody levels and the occurrence of postoperative AF can be viewed as the demonstration of the important role that these proinflammatory antibodies may play in the pathogenesis of AF after coronary artery bypass graft surgery.
In view of the above-mentioned facts, we believe our study not only supports the importance of known risk factors for postoperative AF but also provides novel insights into the possible role of inflammation and cross-reactive autoimmunity in its pathogenesis.1
Mandal K, Jahangiri M, Mulhin M, Poloniecki J, Camm AJ, Xu Q. Association of anti–heat shock protein 65 antibodies with development of postoperative atrial fibrillation. Circulation. 2004; 110: 2588–2590.
Ascione R, Caputo M, Calori G, Lloyd CT, Underwood MJ, Angelini GD. Predictors of atrial fibrillation after conventional and beating heart coronary surgery: a prospective, randomized study. Circulation. 2000; 102: 1530–1535.
Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A, Possati G. The −174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation: is atrial fibrillation an inflammatory complication? Circulation. 2003; 108: II-195–II-199.