Antonios Kourliouros

Dose-Related Effect of Statins on Atrial Fibrillation After Cardiac Surgery

BACKGROUND Atrial fibrillation (AF) is the most common heart rhythm abnormality after cardiac surgery. It increases morbidity and prolongs hospital stay. A role for statins in the prevention of AF has been suggested. We hypothesized that the incidence of postoperative AF due to statin therapy is dose-related. METHODS A retrospective study of 680 consecutive patients undergoing coronary bypass graft surgery and/or aortic valve replacement was done. Excluded were 57 patients (8.4%) with history of AF, permanent pacemakers, and those receiving antiarrhythmic medication. Preoperative statin treatment and occurrence of postoperative AF were examined using propensity score matching to adjust for differences in patient characteristics between the statin and no-statin groups. RESULTS The cohort comprised 623 patients. The statin group had a 27.1% incidence of postoperative AF vs 38.3% in the no-statin group (adjusted odds ratio [OR], 2.00; 95% confidence interval, 1.24 to 3.24; p = 0.004). Simvastatin (40 mg) and atorvastatin (40 mg) demonstrated the greatest effect on postoperative AF at 15.6% and 21.2%, respectively, vs no statins (respective adjusted ORs, 3.89 [p < 0.0001] and 2.76 [p = 0.012]). Intermediate-dose (20 mg) statins were also effective against AF, at 24.4% for simvastatin (adjusted OR, 2.32; p = 0.004) and 26.4% for atorvastatin (adjusted OR, 1.99, p = 0.047). Low-dose statins, simvastatin or atorvastatin (10 mg), did not influence postoperative AF. CONCLUSIONS Statin treatment may reduce the incidence of AF after cardiac surgery. Higher-dose statins have the greatest preventative effect, whereas low-dose statins do not influence postoperative AF.

Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery? A meta-analysis of randomised controlled trials

Background Postoperative atrial fibrillation (POAF) affects approximately 30% of patients undergoing elective cardiac surgery. While its pathogenesis is multifactorial, increasing evidence supports a role for oxidative stress in the electrophysiological remodelling associated with AF. Although prophylactic antioxidants appear to be a potentially attractive pharmacotherapy, there is still uncertainty regarding their efficacy. This study aims to provide a quantitative summary of the current evidence surrounding antioxidant vitamins and POAF prevention. Methods A systematic literature review identified five randomised controlled trials incorporating 567 patients (n=284 antioxidant, n=283 control). These were meta-analysed using random effects modelling. Heterogeneity, subgroup analysis, quality scoring and risk of bias were assessed. Primary endpoints were the incidence of POAF and all-cause arrhythmia. Secondary endpoints were length of stay in the intensive care unit (ITU) and length of hospital stay. Results Vitamins C and E significantly reduced the incidence of POAF (OR 0.43, 95% CI 0.21 to 0.89) and all-cause arrhythmia (OR 0.54, 95% CI 0.29 to 0.99) compared with controls. A significant reduction in both ITU stay (weighted mean difference (WMD) −0.44, 95% CI −0.70 to −0.17) and hospital stay (WMD −1.11, 95% CI −1.70 to −0.52) was also seen in the antioxidant group, without significant heterogeneity. Conclusions The prophylactic use of vitamins C and E may significantly reduce the incidence of POAF and all-cause arrhythmia following cardiac surgery. However, the overall quality of current studies is poor and further research should focus on adequately powered randomised controlled trials that standardise AF reporting, antioxidant protocol and the use of concomitant agents. Cost analysis should be considered to establish the potential economic benefit of antioxidant vitamin prophylaxis in POAF.

Low cardiopulmonary bypass perfusion temperatures are associated with acute kidney injury following coronary artery bypass surgery.

OBJECTIVE Acute kidney injury (AKI) is a common complication after coronary artery bypass surgery (CABG). The role of hypothermia in postoperative renal function remains controversial. We set out to examine the effect of varying cardiopulmonary bypass (CPB) temperatures on early postoperative renal function. METHODS Patients undergoing first-time CABG between 2002 and 2006 and without evidence of preoperative renal insufficiency (estimated creatinine clearance >or=50 ml min(-1), calculated by the Cockcroft-Gault formula) were studied. Medical history and intra-operative variables, including lowest nasopharyngeal and arterial CPB perfusion temperatures, were collected prospectively. Primary endpoint was the development of early postoperative AKI (defined as creatinine clearance <50 ml min(-1)), which was assessed using multivariate and propensity score analyses. RESULTS This study included 1072 patients. AKI occurred in 175 (16%). Univariate analysis demonstrated that lower arterial CPB perfusion temperatures, and not nasopharyngeal ones, were significantly associated with renal dysfunction following CABG. Multivariate regression analysis identified reduced arterial perfusion temperature as an independent risk factor for AKI (odds ratio (OR) 0.92, 95% confidence interval (CI): 0.86-0.98, p=0.012), along with age (OR 1.07, 95% CI: 1.04-1.10, p<0.001) and depressed preoperative creatinine clearance (OR 0.89, 95% CI: 0.87-0.91, p<0.001). Propensity score adjustment confirmed that lower CPB perfusion temperatures (<27 degrees C) were associated with postoperative AKI (OR 1.66, 95% CI: 1.16-2.39, p=0.0056). CONCLUSIONS Lower CPB perfusion temperatures are significantly associated with AKI following CABG. In addition to the known age-related decline in renal function, it appears that hypothermia may contribute to renal injury during cardiac surgery.

Protective effect of epicardial adiponectin on atrial fibrillation following cardiac surgery

OBJECTIVE Inflammation has been implicated in the pathogenesis of postoperative atrial fibrillation (AF). Adipose tissue secretes both pro-inflammatory cytokines such as interleukin-6 (IL-6) and anti-inflammatory mediators such as adiponectin. We set out to examine the association of adiponectin and IL-6, both circulating and locally produced by the epicardial adipose tissue, with AF development after cardiac surgery. METHODS A total of 90 consecutive patients undergoing cardiac surgery were evaluated. Blood samples were collected before induction of anaesthesia. Epicardial fat was obtained upon commencement of cardiopulmonary bypass. IL-6 and adiponectin levels were determined in serum and supernatant of epicardial adipose tissue organ cultures with two-site enzyme-linked immunosorbent assay (ELISA). Heart rhythm was assessed with continuous tele-monitoring for 72 h postoperatively, and with 6-hourly clinical examinations and daily electrocardiograms (ECGs) thereafter. RESULTS A total of 36 patients developed postoperative AF (40%). Baseline-serum IL-6 and adiponectin were not associated with AF (p = 0.86 and 0.95, respectively). Epicardial adipose tissue IL-6 levels did not correlate with the development of the arrhythmia either (p = 0.37). However, epicardial adiponectin release was lower in patients who developed AF than in those who remained in sinus rhythm (76 (interquartile range (IQR) 35-98) vs 53 ((IQR) 35-69) ng h(-1)g(-1) of tissue cultured, p = 0.066). Following linear regression, the association of epicardial adiponectin with AF almost reached statistical significance (p = 0.066). Multivariate logistic regression analysis of identified risk factors for AF, with the inclusion of epicardial adiponectin as an independent variable, revealed increased age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.17, p = 0.013) and epicardial adiponectin levels (OR 0.98, 95% CI 0.97-1.00, p = 0.054) as independent predictors of postoperative AF. CONCLUSIONS Increased epicardial adiponectin is associated with maintenance of sinus rhythm following cardiac surgery. This reinforces the inflammatory hypothesis in the pathogenesis of postoperative AF and may represent a novel therapeutic target for its effective prevention.

Preoperative high-dose atorvastatin for prevention of atrial fibrillation after cardiac surgery: A randomized controlled trial

OBJECTIVE The preventative effect of statins on postoperative atrial fibrillation has been hypothesized. However, all studies to date have examined patients who did not receive statins before their further allocation to treatment or no treatment. Because guidelines recommend the routine use of statins in patients with coronary artery disease, we set out to examine the effect of intensive statin pretreatment versus continuation of usual statin dose on atrial fibrillation after cardiac surgery. METHODS Patients receiving routine statin treatment and undergoing coronary artery bypass surgery or aortic valve replacement with no history of atrial fibrillation or antiarrhythmic medication were randomized to receive atorvastatin 80 mg or atorvastatin 10 mg for 7 days before surgery in a single-blind fashion. The primary end point was the development of postoperative atrial fibrillation during hospital stay. RESULTS A total of 104 consecutive patients were included. Postoperative atrial fibrillation occurred in 33 patients (32.4%). No significant differences were found in demographics, medical history, or intraoperative variables between treatment groups, with the exception of higher rate of β-blocker use in the atorvastatin 10 mg group (75% vs 53%, P = .002) and previous myocardial infarction (62% vs 42%, P = .049). The incidence of postoperative atrial fibrillation was lower in the atorvastatin 80 mg group when compared with the atorvastatin 10 mg group, but this difference did not reach statistical significance (29% vs 36%, P = .43). CONCLUSIONS High-dose atorvastatin for 7 days before cardiac surgery conferred a nonsignificant reduction in postoperative atrial fibrillation when compared with a low-dose regimen. A larger study would be necessary to confirm the beneficial effect of high-dose statins in this setting.

Antioxidant vitamins in the prevention of atrial fibrillation: what is the evidence?

Atrial fibrillation (AF) is the most common sustained arrhythmia that is associated with significant morbidity and mortality. Current available therapies remain inadequate in symptom control and secondary prevention and are often associated with significant side effects. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. Recently, increasing evidence implicates oxidative stress and inflammation in the pathogenesis of AF. We searched the literature for evidence to support the use of antioxidant vitamins C and E in the prevention of AF. These vitamins, through their reactive-oxygen-species- (ROS-) scavenging effect, have shown a role in AF prevention in both animal and small clinical studies. The available evidence, however, is currently insufficient to support recommendations for their use in the wider patient population. Larger-scale clinical studies are required to confirm these preliminary results. Research is also required to further the understanding of the processes involved in the pathogenesis of AF and the role of antioxidant therapies to prevent the arrhythmia.

Prediction of postoperative left ventricular systolic function in patients with chronic mitral regurgitation undergoing valve surgery — the role of deformation imaging

OBJECTIVE Preoperative left ventricular systolic function is an important prognostic factor in patients undergoing mitral valve surgery. Preoperative myocardial deformation may be impaired without reduction in conventional indices such as ejection fraction (EF). Strain rate (SR) imaging is very sensitive in detecting regional systolic abnormalities and might allow diagnosis of subclinical changes in systolic left ventricular (LV) function before surgery. We aimed to investigate the value of preoperative regional myocardial peak systolic SR as a predictor of postoperative LV systolic function in patients with severe mitral regurgitation (MR) undergoing surgery. METHODS A total of 62 patients (age 52±12) with chronic severe MR, who underwent mitral valve repair, were studied. A standard echo examination, extended with tissue Doppler, was performed before and at 12 months after surgery. For the evaluation of longitudinal function, mid-ventricular segment shortening was analysed for the septum, LV lateral wall and anterior and inferior walls. RESULTS Patients were divided into two groups based on postoperative EF: group 1 with EF(post-op)>50% and group 2 with EF(post-op)<50%. Group 1 had a significantly (p=0.004) higher preoperative SR (LV lateral wall: -1.97±0.26s(-1); septum: -1.74±0.31s(-1); anterior wall: -1.94±0.30s(-1), inferior wall: -1.93±0.29s(-1)) compared to group 2 (LV lateral wall: -0.98±0.23s(-1); septum: -0.98±0.26s(-1); anterior wall: -0.94±0.30s(-1), inferior wall: -1.00±0.24s(-1)). When SR was corrected for size, the SR/EDV index (EDV is end diastolic volume) also showed significant changes (p=0.0007) at baseline between the groups. For detecting subclinical changes in deformation of the LV lateral wall, a cut-off value of the SR/EDV index<0.006 had 89% sensitivity and 93% specificity; for the anterior wall, SR/EDV index<0.005 had 88% sensitivity and 94% specificity. CONCLUSIONS SR imaging (corrected for geometry) can detect abnormalities in LV function at subclinical levels in patients with severe mitral regurgitation.

Substrate Modifications Precede the Development of Atrial Fibrillation After Cardiac Surgery: A Proteomic Study

BACKGROUND Atrial fibrillation (AF) is an important cause of morbidity and mortality after cardiac surgery. The pathogenesis of AF appears to be multifactorial but little is known about the cause-effect relationship of substrate modifications with the onset of the arrhythmia. With the use of modern proteomics, this study aims to identify preexisting changes in the left atrium of patients susceptible to postoperative AF. METHODS We analyzed 20 matched patients undergoing elective, first-time coronary artery bypass grafting with no history of AF. They were divided into 2 equal groups according to the development of postoperative AF. Proteomic analysis was performed in left atrial tissue obtained during surgery using two-dimensional difference in gel electrophoresis techniques. Mass spectrometry identified proteins that were differentially expressed in patients who developed AF against those who remained in sinus rhythm. RESULTS Proteomic analysis of left atrial tissue identified 19 differentially expressed protein spots between patients who developed postoperative AF and their sinus rhythm counterparts. In patients who developed AF, proteins associated with oxidative stress and apoptosis (peroxiredoxin 1, apoptosis-inducing factor, and 96S protease regulatory subunit 8) as well as acute phase response components (apolipoprotein A-I, fibrinogen) were found to be increased. Conversely, the expression of proteins responsible for glycolysis (enolase) and pyruvate metabolism (pyruvate dehydrogenase) was reduced. CONCLUSIONS We describe protein changes that precede the development of postoperative AF and which might be suggestive of increased oxidative stress and glycolytic inhibition in the left atrium of patients predilected to AF.

Intra-operative conversion is a cause of masked mortality in off-pump coronary artery bypass: a meta-analysis

Coronary artery bypass surgery can offer excellent results when performed with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). The debate as to which technique is superior remains unanswered. Intra-operative conversion from off- to on-pump coronary surgery is a relatively unexplored phenomenon, which cannot be assessed within randomised controlled trial design. We aimed to assess the effect of off-pump conversion on patient mortality. Medline, Embase, Cochrane and Google Scholar databases were systematically reviewed for studies published between 1980 and 2010 that compared the incidence of mortality between converted and non-converted off-pump patients. Publication bias and heterogeneity were assessed and data were extracted independently by multiple observers. We undertook a meta-analysis of these studies using random effects modelling. A total of 17 studies fulfilled our inclusion criteria, containing data for 18,870 off-pump coronary artery bypass operations spanning a decade (1998-2008), involving 920 cases of conversion. Overall, conversion increased mortality by an odds ratio of 6.18 (95% confidence interval 4.65-8.20), whereas emergency conversion further raised the odds ratio of mortality to 6.99 (95% confidence interval 5.18-9.45). The conversion from off- to on-pump cardiac surgery may significantly increase the chance of an adverse outcome, whereas emergency conversion confers a significant rise in mortality. The risk of conversion should be discussed when obtaining the patients informed consent and its prevention warrants serious consideration by cardiac surgeons and cardiac surgical training programmes.

Strategies in the Surgical Management of Atrial Fibrillation

Atrial fibrillation (AF) is associated with substantial morbidity, mortality, and economic burden and confers a lifetime risk of up to 25%. Current medical management involves thromboembolism prevention, rate, and rhythm control. An increased understanding of AF pathophysiology has led to enhanced pharmacological and medical therapies; however this is often limited by toxicity, variable symptom control, and inability to modulate the atrial substrate. Surgical AF ablation has been available since the original description of the Cox Maze procedure, either as a standalone or concomitant intervention. Advances in novel energy delivery systems have allowed the development of less technically demanding procedures potentially eliminating the need for median sternotomy and cardiopulmonary bypass. Variations in the definition, duration, and reporting of AF have produced methodological limitations impacting on the validity of interstudy comparisons. Standardization of these parameters may, in future, allow us to further evaluate clinical endpoints and establish the efficacy of these techniques.