Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation

Mandal, Kaushik; Jahangiri, Marjan; Mukhin, Michael; Poloniecki, Jan; Camm, A. John; Xu, Qingbo

doi:10.1161/01.cir.0000136825.96029.a5

Cited by 40 publications

(21 citation statements)

References 21 publications

(17 reference statements)

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“…The median age was 65 years (40–80 years). Exclusion criteria were preceding history of AF, other associated operations, acute coronary event within 6 weeks before surgery, active infection, history of autoimmune diseases, and use of immunosuppressive drugs [27]. Demographic data, cardiovascular risk factors, and usage of medications, e.g.…”

Section: Methodsmentioning

confidence: 99%

Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels

et al. 2007

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Background: Atrial fibrillation (AF) is a common arrhythmia encountered following cardiac surgery. Previously, we have shown that higher expression of heat shock protein (HSP) 70 was associated with decreased incidence of postoperative AF (PoAF), suggestive of an antiarrhythmic role. Objective: We have hypothesised that Met493Thr substitution of one of the important hsp70 genes may cause loss of these protective antiarrhythmic effects. We therefore set out to examine the influence of hsp70 genotype on the incidence of PoAF. Methods and Results: We prospectively recruited 244 Caucasian patients undergoing elective coronary artery bypass surgery. The median age was 65 years (40–80 years). PoAF was defined as the characteristic arrhythmia lasting for at least 15 min, occurring within first week following surgery and requiring treatment. This occurred in 48 patients (19.7%). Validated Met493Thr substitution in hsp70-Hom was determined using established techniques. Of 244 patients, genotype was determined for 242 cases. The three genotypes (MM, MT, and TT) were present at frequencies of 0.66, 0.31, and 0.03, respectively, and were in Hardy-Weinberg equilibrium. In unifactorial analysis patients carrier or homozygous for 493Thr mutation had significantly higher incidence of PoAF (Pearson χ² = 4.3, p = 0.037). Multivariate analysis confirmed the positive association of hsp70-Hom with PoAF (OR, 2.43; p = 0.016) independent of age, sex, previous myocardial infarction, number of distal anastomoses, and duration of ventilation, respectively. Serum HSP70 was ranging from 0.74 to 31.91 ng/ml (median, 2.89) and was not correlated with PoAF. Presence of 493Thr mutation was also significantly correlated with higher levels of serum HSP70 (p = 0.009). Conclusions: Our data show that a mutation in hsp70-Hom gene is associated with higher incidence of PoAF. These findings are consistent with our previous results and may suggest that patients harbouring this substitution will have less endogenous myocardial protection against AF in stressful situations.

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Section: Methodsmentioning

confidence: 99%

Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels

et al. 2007

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“…13 Maixent and colleagues 15 speculated on the possibility of an autoimmune process after finding circulating antimyosin autoantibodies in the serum of patients who had lone AF. Mandal and associates 17 investigated the effects of heat-shock proteins (HSPs), a group of chaperone proteins that preserve cellular integrity by keeping proteins in their correctly folded state. Their study showed that the inflammationinduced expression of HSPs on the surface of myocytes might lead to cell lysis by circulating anti-HSP65 antibodies, with subsequent structural myocardial changes leading to AF after cardiac surgery.…”

Section: Correlation Between Atrial Fibrillation and Inflammationmentioning

confidence: 99%

Inflammation and C-Reactive Protein in Atrial Fibrillation: Cause or Effect?

Galea¹,

Cardillo²,

Caroli³

et al. 2014

Texas Heart Institute Journal

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“…1 We agree that ␤-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 ␤-blockers in the postoperative period that makes these patients more prone to postoperative AF.…”

Section: Responsementioning

confidence: 55%

Letter Regarding Article by Mandal et al, “Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation”

2005

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Mandal and colleagues 1 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 ␤-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][3][4][5] In addition, previous studies and reviews 2 consistently found that preoperative ␤-blocking agents protect against postoperative AF.Because the present study is in contrast with previous data on the association between age, preoperative ␤-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. Johann Auer, MD Gudrun Lamm, MD Thomas Weber, MDGeneral Hospital Wels, Austria johann.auer@khwels.at ResponseWe thank Dr Auer and colleagues for their interest in our article. 1 We agree that ␤-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 ␤-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 ␤-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 (65Ϯ7 years versus 64Ϯ9 years; Pϭ0.14). 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 occurre...

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Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation

Cited by 40 publications

References 21 publications

Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels

Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels

Inflammation and C-Reactive Protein in Atrial Fibrillation: Cause or Effect?

Letter Regarding Article by Mandal et al, “Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation”

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