Do technical parameters affect the diagnostic accuracy of virtual bronchoscopy in patients with suspected airways stenosis?

PURPOSE: Virtual bronchoscopy has gained popularity over the past decade as an alternative investigation to conventional bronchoscopy in the diagnosis, grading and monitoring of airway disease. The effect of technical parameters on diagnostic outcome from virtual bronchoscopy has not been determined. This meta-analysis aims to estimate accuracy of virtual compared to conventional bronchoscopy in patients with suspected airway stenosis, and evaluate the influence of technical parameters. MATERIALS AND METHODS: A MEDLINE search was used to identify relevant published studies. The primary endpoint was the "correct diagnosis" of stenotic lesions on virtual compared to conventional bronchoscopy. Secondary endpoints included the effects of the technical parameters (pitch, collimation, reconstruction interval, rendering method, and scanner type), and date of publication on the diagnostic accuracy of virtual bronchoscopy. RESULTS: Thirteen studies containing 454 patients were identified. Meta-analysis showed good overall diagnostic performance with 85% calculated pooled sensitivity (95% CI 77-91%), 87% specificity (95% CI 81-92%) and area under the curve (AUC) of 0.947. Subgroups included collimation of 3mm or more (AUC 0.948), pitch of 1 (AUC 0.955), surface rendering technique (AUC 0.935), and reconstruction interval of more than 1.25 mm (AUC 0.914). There was no significant difference in accuracy accounting for publication date, scanner type or any of the above variables. Weighted regression analysis confirmed none of these variables could significantly account for study heterogeneity. CONCLUSION: Virtual bronchoscopy performs well in the investigation of patients with suspected airway stenosis. Overall sensitivity and specificity and diagnostic odds ratio for diagnosis of airway stenosis were high. The effects of pitch, collimation, reconstruction interval, rendering technique, scanner type, and publication date on diagnostic accuracy were not significant.

Should the internal thoracic artery be skeletonized?

Traditionally, the internal thoracic artery is harvested as a pedicle. In contemporary cardiac surgical practice, however, certain surgeons practice the internal thoracic artery-skeletonization technique. A systematic review of clinical studies reporting on the use of skeletonized internal thoracic arteries (SKT-ITA) has not yet been performed. The primary aim of this review article is to examine comprehensively the entire body of evidence regarding the use of SKT-ITA. In particular, we aimed to analyze the effects of skeletonization on sternal blood supply, wall damage and blood flow in the harvested vessel, postoperative graft patency, and clinical outcome. Advantages and disadvantages of the skeletonization technique are highlighted and discussed.

Is the female gender an independent predictor of adverse outcome after off-pump coronary artery bypass grafting?

BACKGROUND: The female gender is an independent predictor of adverse outcome after conventional coronary artery bypass grafting using cardiopulmonary bypass. The aim of this study is to assess the effect of the female gender on the outcome after off-pump coronary artery bypass (OPCAB) surgery. METHODS: This study is a retrospective review of 413 consecutive patients (181 women and 232 men) who underwent OPCAB between January 1999 and May 2001. Adverse outcomes were divided into minor adverse outcomes (MINAO), major adverse outcomes (MAJAO), and prolonged length of stay (PLOS) more than 7 days. MINAO included atrial fibrillation, respiratory complications except adult respiratory distress syndrome, and any wound infection except mediastinitis. MAJAO included stroke, myocardial infarction, renal failure, adult respiratory distress syndrome, mediastinitis, low cardiac output, mechanical ventilation more than 24 hours, intensive therapy unit stay more than 24 hours, gastrointestinal complications, cardiorespiratory arrest, and mortality within 30 days. Preoperative and intraoperative variables were evaluated as predictors of MINAO, MAJAO, and PLOS by univariate and multivariate analyses. RESULTS: The groups were matched for age and Parsonnet score-predicted mortality. However, the women had a higher incidence of chronic obstructive airway disease (p = 0.04), diabetes (p = 0.01), obesity (p = 0.000), peripheral vascular disease (p = 0.000), hypertension (p = 0.000), unstable angina (p = 0.005), history of previous failed nonsurgical intervention (p = 0.02), and nonelective operation (p = 0.000). There were a fewer number of grafts performed in the female group (2.8 vs 3.4, p = 0.000), with the circumflex territory being revascularised less frequently (p = 0.001). Univariate analysis identified the female gender to be a predictor of only MINAO (p = 0.001) and PLOS (p = 0.000). However, with multivariate analysis, female gender was not found to be an independent predictor of MINAO, MAJAO, or PLOS. CONCLUSIONS: In OPCAB, the female gender is not an independent predictor of MINAO, MAJAO, or PLOS.

Expanded use of suction and stabilization devices in cardiothoracic surgery.

BACKGROUND: Recent developments in beating heart instrumentation have allowed surgeons to perform multivessel off-pump coronary artery bypass surgery by overcoming the factors that impair surgical performance (limited visualization, continuous movement of the target area, and hemodynamic instability during exposure of the inferior and posterior parts of the heart). We have explored the possibility of further expanding apical and epicardial suction devices beyond their ordinary use in coronary artery surgery. METHODS: A retrospective review of our cardiac surgery database was undertaken to identify the incidences in which these devices have been used in a somewhat novel manner in the field of cardiac surgery. RESULTS: During this time period we identified 20 instances in which either apical or epicardial suction devices were used alone or together. The nature of the procedures included dividing pericardial adhesions (pericardiectomy, n = 2; dividing adhesions in redo-coronary surgery, n = 4), securing epicardial hemostasis (penetrating cardiac trauma, n = 2; securing hemostasis during reexploration after cardiac surgery, n = 10), and facilitating epicardial microwave ablation (n = 2). On all 20 occasions the intended procedures were undertaken uneventfully. Furthermore, the use of apical and epicardial devices greatly facilitated the operative procedures and avoided the use of cardiopulmonary bypass on all occasions. CONCLUSIONS: In summary, we would like to highlight the expanding role for apical and epicardial suction devices to an area beyond coronary artery surgery in which we have found their use invaluable.

Do off-pump techniques reduce the incidence of postoperative atrial fibrillation in elderly patients undergoing coronary artery bypass grafting?

BACKGROUND: Atrial fibrillation is the most common postoperative complication in patients undergoing coronary artery bypass grafting (CABG) with advancing age having been shown to have a significant association with its incidence. This study aims to assess whether off-pump coronary artery bypass (OPCAB) reduces the incidence of atrial fibrillation in elderly patients. METHODS: A meta-analysis of all observational studies reporting a comparison between the two techniques in elderly patients (> 70 years) between 1999-2003 was performed. The primary outcome of interest was the incidence of postoperative atrial fibrillation. The quality of each study was evaluated by examining three items: patient selection, matching of the off-pump and cardiopulmonary bypass patient groups, and assessment of outcome. Meta-regression analysis was undertaken to see the effects of study size and quality on the calculated odds ratio. RESULTS: Eight studies fulfilled our inclusion criteria, all of which were nonrandomized. In total the studies identified 3017 subjects, of which 764 had off-pump surgery (25%) and 2253 underwent cardiopulmonary bypass (75%). Meta-analysis showed that after off-pump surgery there was a significantly lower incidence of postoperative atrial fibrillation in these patients (odds ratio 0.70, 95% confidence interval [CI] 0.56-0.89). Meta-regression analysis including study characteristics did not show any associations affecting the calculated odds ratio of atrial fibrillation. CONCLUSIONS: Our study demonstrates a reduced incidence of postoperative atrial fibrillation in an elderly population with off-pump as compared with cardiopulmonary bypass techniques. We appreciate, however, that our statistical analysis uses nonrandomized published data and that the results must be treated with caution. If this finding is confirmed by a large-scale randomized trial, it has significant implications on the operative strategy employed for this patient group.

Leg wound infection after coronary artery bypass grafting: a meta-analysis comparing minimally invasive versus conventional vein harvesting.

The great saphenous vein remains the most commonly harvested conduit for revascularization in coronary artery bypass grafting (CABG). Our aim is to compare minimally invasive vein harvest techniques to conventional vein harvest with regards to leg wound infection rates. A meta-analysis of identified randomized controlled trials, reporting a comparison between the two techniques published between 1965 and 2002, was undertaken. The outcome of interest was leg wound infection. Fourteen randomized studies were identified and included in the meta-analysis. Our study revealed that wound infection was significantly lower in the minimally invasive vein harvest group (odds ratio 0.22 with 95% confidence intervals of 0.14 to 0.34). Our study suggests that using minimally invasive techniques might reduce leg wound infection rate following great saphenous vein harvesting for CABG. Further research is required to evaluate the potential benefits of minimally invasive vein harvesting techniques on the cost of postoperative care and quality of the harvested vein.

Off-pump myocardial revascularization is associated with less incidence of stroke in elderly patients.

Several recent studies have highlighted the potential benefits of using off-pump coronary artery bypass (OPCAB) surgery, particularly in high-risk patients. The aim of this meta-analysis is to assess the effect of OPCAB on the incidence of stroke compared with coronary artery bypass grafting using cardiopulmonary bypass (CPB) in elderly patients. We performed a meta-analysis of all observational studies, published in MEDLINE between 1999 and 2002 and a comparison between the OPCAB and CPB techniques in elderly patients was performed with the outcome of interest being the incidence of stroke. Elderly patients were defined as those aged 70 years or older. Nine studies are included in the meta-analysis. The total number of subjects included was 4,475 patients, of which, 1,253 underwent OPCAB (28%) and 3,222 (72%) underwent CPB. The meta-analysis showed that the OPCAB technique was associated with significantly lower incidence of stroke in elderly patients compared with the CPB technique (1% vs 3%), with an odds ratio of 0.38% to 95% (CI, 0.22 to 0.65). We did not identify any significant heterogeneity and funnel plot asymmetry between the studies included in the meta-analysis. Meta-regression analysis including variables predicting stroke, mortality, and study characteristics did not show any associations affecting the calculated odds ratio of stroke. Despite the fact that this is a meta-analysis of observational studies and adjustment for differences in baseline risk factors between OPCAB and CPB patients was not possible, we believe that this study suggests that the OPCAB technique might be associated with reduced incidence of stroke in the elderly patients undergoing coronary artery bypass grafting.

Is the use of cardiopulmonary bypass for multivessel coronary artery bypass surgery an independent predictor of operative mortality in patients with ischemic left ventricular dysfunction?

BACKGROUND: l Coronary artery bypass grafting for patients with ischemic left ventricular dysfunction (ILVD) remains superior to medical therapy in terms of long-term survival. Recently, off-pump coronary artery bypass surgery has been shown to be very promising in achieving functional improvements with favorable operative mortality in this challenging group of patients. The aim of this study was to assess the risk factors responsible for operative mortality in this group of patients. METHODS: The records of 305 consecutive ILVD patients, who underwent primary isolated coronary artery bypass grafting for multivessel disease at The National Heart and Lung Institute, Imperial College, University of London, between January 1999 and January 2002, were reviewed retrospectively. Patients were considered to have ILVD if they had a left ventricular ejection fraction of 0.30 or less on preoperative coronary angiography. One hundred six patients were operated on using the off-pump coronary artery bypass surgery technique, and 199 patients were operated on using the conventional coronary artery bypass grafting technique with cardiopulmonary bypass. RESU;TS: Seven (6.6%) patients died in the off-pump coronary artery bypass surgery group, whereas 28 (14.1%) patients died in the cardiopulmonary bypass group (p = 0.05). Univariate analysis of all the preoperative characteristics was performed to identify the potential predictors of mortality in the whole group of ILVD patients. Potential predictors of mortality included symptom status (stable/unstable), chronic obstructive airway disease, dyspnea grade III and IV on the New York Heart Association classification, intravenous nitrates, preoperative use of intraaortic balloon pump, ventricular tachycardia or ventricular fibrillation, body surface area less than 2, and cardiopulmonary bypass. Only ventricular tachycardia or ventricular fibrillation was proved to act as an independent predictor of operative mortality in this group of ILVD patients, with an odds ratio of 29.6 (95% confidence interval, 8.9 to 98). CONCLUSIONS: This study showed that using cardiopulmonary bypass for multivessel coronary artery bypass grafting in patients with ILVD was not proved to act as an independent predictor of operative mortality.

Are wound healing disturbances and length of hospital stay reduced with minimally invasive vein harvest? A meta-analysis.

Minimally invasive great saphenous vein harvest for coronary artery bypass grafting aims to reduce post-operative leg-wound related morbidity. In a meta-analysis of randomised trials we have shown leg wound infection rates to be significantly lower in patients undergoing minimally invasive harvest. This study aims to use meta-analysis to compare the two techniques with regards to non-infective wound healing disturbances (NIWHD) (wound drainage, haematoma, dehiscence, necrosis, need for surgical debridement, and seroma formation). A meta-analysis of all studies published between 1995 and 2002 reporting a comparison between the two techniques was performed. Primary outcomes of interest were the six wound healing disturbances mentioned above and length of hospital stay. Heterogeneity was assessed using graphical exploration and sensitivity analysis with subgroup analysis. Twenty-seven studies published between 1997 and 2002 matched our selection criteria, with a combined total of 4953 subjects, of which 2442(49%) underwent minimally invasive harvest and 2511(51%) underwent conventional surgery. When considering only randomised studies, the total number of non-infective wound disturbances was lower in minimally invasive (4%) as compared to the conventional (13%) group (random effect OR 0.24, CI 0.16-0.38). Similar results were found when only fully matched studies were considered. The absolute risk reduction when comparing the two techniques was calculated to be 0.10, which translates to a number of patients needed to treat of 10. Length of stay was significantly reduced in the minimally invasive group in comparison to the conventional group (random effect weighted mean difference of -1.04, CI -1.92 to -0.16). Our results suggest that NIWHD all reduced with minimally invasive harvest techniques. Despite the limitations of this meta-analysis, we feel we have once again illustrated an important link between minimally invasive great saphenous vein harvest and improved tissue healing when compared to conventional open surgery. This has the potential to reduce wound-related morbidity, infection, post-operative pain, length of hospital stay, and re-admission rate.

Does off-pump coronary artery bypass reduce the incidence of post-operative atrial fibrillation? A question revisited.

Atrial fibrillation (AF) is the most common post-operative complication in patients undergoing coronary artery bypass grafting, with an increased incidence associated with advancing age. This study aims to determine whether off-pump coronary artery bypass (OPCAB) reduces the incidence of AF in a generalized population (mean age <70 years). A meta-analysis was performed including all randomised and propensity score matched non-randomised studies published between 2001 and 2003 reporting a comparison between the two techniques in a generalised patient group (average age <70 years). The primary outcome of interest was post-operative AF. Sensitivity analysis was performed to evaluate consistency of the calculated treatment effect. Fourteen studies fulfilled our inclusion criteria, including a total of 16,505 subjects. The incidence of AF was 19% (1612/8265) in the off-pump group versus 24% (1976/8240) in the on-pump group. When considering only the 11 randomised studies (2207 subjects), we found a significant reduction in the incidence of post-operative AF in the off-pump group using a random-effect model (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.45-0.82, and chi-square of heterogeneity=18.02, P=0.05). Sensitivity analysis highlighted one randomised study causing funnel plot asymmetry, exclusion of which resulted in a significant reduction in the incidence of post-operative AF in the off-pump group (OR=0.71, 95% CI=0.57-0.90), with a non-significant heterogeneity of 3.91 (P=0.92). When only studies of high quality were considered (898 patients), no significant difference was seen between on and off-pump groups (OR=0.78, 95% CI=0.57-1.07, and heterogeneity=0.53, P=0.91). This may be due to small number of patients in this group. Our results suggest that although OPCAB surgery may reduce the incidence of post-operative AF in a generalised population (age <70 years) this finding is not clearly supported by high quality randomised trials. Although previous evidence suggests that the incidence of post-operative AF is reduced in an elderly population (>70 years) with off-pump surgery, our results show that the evidence is less clear in a younger population group. The question of whether off-pump surgery in this patient group results in a lower rate of post-operative AF remains to be answered by further high quality randomised research.

Coronary artery bypass with the use of a magnetic distal anastomotic device: surgical technique and preliminary experience.

BACKGROUND: At present there is little reported experience in the application of new technology in the performance of distal coronary anastomoses in the clinical setting. The aim of our study was to evaluate the feasibility of using the Ventrica magnetic vascular positioner (MVP) device for left internal thoracic artery (LITA)-to-left anterior descending (LAD) coronary anastomosis. METHODS: We present our preliminary experience of the first 14 coronary artery cases performed in the United Kingdom from April 2003 to December 2003. The selection criteria, surgical technique, clinical outcome, advantages or disadvantages, and future implications are all discussed. RESULTS: The device was used in 12 patients for LITA-to-LAD anastomosis and in 2 patients for the proximal anastomosis of a radial artery Y-graft from the LITA to the circumflex territories. The first 3 patients underwent coronary artery bypass graft with the use of cardiopulmonary bypass, and the remaining 9 underwent surgery performed using an off-pump coronary artery bypass technique. No mortality or device-related events were observed in these patients. The anastomosis time in our series was 5.6 +/- 1.99 minutes, and the blood loss was 914 +/- 234 mL. The mean length of stay was 5.8 +/- 1.16 days. CONCLUSION: The MVP system is a novel distal coronary anastomotic device that is quick, simple, and effective, producing consistently reliable coronary anastomoses in a wide variety of coronary bypass procedures. Early results are encouraging, and further studies are required in order to evaluate long-term efficacy of this system in the rapidly changing world of coronary revascularization.

How I do it: a new method of myocardial revascularization with use of the radial loop technique.

We report a technique that allows total arterial myocardial revascularization of the left ventricle by the use of the radial artery as a composite graft. The technique includes anastomosis of the distal end of the radial artery to its more proximal part after division of the conduit from the brachial artery. In this way we create an adjustable loop that can be divided and used as a Y-fashioned conduit according to the needs of revascularization. The main advantages of this technique are that it saves time and facilitates complex arterial revascularization of the lateral and posterior parts of the left ventricle, especially during off-pump revascularization. At least 2 coronary targets can be revascularized with the radial artery in a flexible and safe manner. The radial artery also has important potential opportunities for multiple grafting through minimal-access incisions or endoscopic coronary artery bypass grafting when a critical Y anastomosis is needed inside the chest.

Pituitary apoplexy and CABG: should we change our strategy?

Patients with pituitary adenoma that had coronary artery bypass grafting with cardiopulmonary bypass had pituitary apoplexy develop with neurologic deficits and even death. Four patients with pituitary adenoma underwent coronary artery bypass grafting operations (3 patients had coronary artery bypass grafting on bypass, 1 of them with known pituitary adenoma. All of them had pituitary apoplexy develop with neurologic deficits). One patient with known pituitary adenoma who had a coronary artery bypass grafting operation off pump was neurologically intact. Our recommendation is to consider operating on patients with pituitary adenoma who need coronary artery bypass grafting operation off pump, and to prevent pituitary apoplexy that cardiopulmonary bypass may cause.

Clampless arterial coronary artery bypass grafting with the use of magnetic coupling devices.

BACKGROUND: The aim of our study was to evaluate the feasibility of using the Ventrica MVP device to perform proximal anastomoses as part of the clampless off-pump coronary artery bypass (OPCAB) arterial revascularization procedure. METHODS: We present our preliminary experience of these first nine coronary artery cases performed in the UK from April 2003 to December 2004. RESULTS: The device was used in eight patients for the proximal anastomosis of a radial artery (n = 8) or right internal thoracic artery (n = 1) graft as a Y-graft from the left internal thoracic artery to the circumflex territories. One patient died in this series although the autopsy showed that the device was intact and free of clots and the reported cause of death was an acute cardiac event due to myocardial ischemia. Anastomotic patency was confirmed in five patients with the use of multidetector row computed tomography coronary angiogram. The anastomosis time in our series was 6.3 +/- 2.1 minutes and the blood loss 814 +/- 245 mL. The mean length of stay was 5.2 +/- 1.2 days. No other significant major morbidity events were observed postoperatively (neurological complications, renal failure, and reopening for bleeding). The assessment of quality of life at 6 months postoperatively using SF-36 questionnaires revealed improvement. CONCLUSION: The versatile use of Ventrica MVP distal anastomotic device is feasible in clinical practice allowing surgeons to perform proximal anastomoses and arterial OPCAB surgery with short learning curve and without compromising the clinical outcome and quality of life.

Functional renal outcome in on-pump and off-pump coronary revascularization: a propensity-based analysis.

BACKGROUND: Since the advent of off-pump coronary artery bypass grafting (OPCAB), comparisons have been made between it and on-pump coronary artery bypass grafting. Some observe a lesser incidence of acute renal failure requiring renal replacement therapy with OPCAB whereas others do not. The objective was to compare the occurrence of renal adverse outcome between on-pump coronary artery bypass grafting and OPCAB. Renal adverse outcome was defined as minor (20% increase in serum creatinine from preoperative) or major (composite end point of postoperative serum creatinine >200 mumol/L or postoperative mechanical renal support). METHODS: The study was based on 2,041 patients with no known preoperative renal disease having first-time isolated coronary artery bypass grafting of multiple coronary arteries between January 2001 and November 2003, at St. Mary's Hospital, Harefield Hospital, and Hammersmith Hospital, in West London; 1,224 patients had on-pump coronary artery bypass grafting and 817 patients had OPCAB. Selection bias for surgical technique was addressed by calculating the propensity score for each patient and using it as an independent variable for adjustment in the multivariate analysis. Univariate and multivariate ordered logistic regressions were used to identify factors associated with renal adverse outcome ordered as none, minor, and major. RESULTS: The number of grafts was 3.22 +/- 0.82 for the on-pump coronary artery bypass grafting group and 3.35 +/- 0.95 for the OPCAB group. On-pump coronary artery bypass grafting and increasing age were found to be the strongest independent predictors (p < 0.001) of renal adverse outcome. Other independent predictors included hypertension (p = 0.005), diabetes (p = 0.032), and preoperative serum creatinine (p = 0.001). A left ventricular ejection fraction of 0.30 to 0.49 (p = 0.099) and an ejection fraction of 0.50 or greater (p < 0.001) were associated with decreased risk compared with patients with an ejection fraction of less than 0.30. Interestingly, the use of non-left internal mammary arterial conduits significantly decreased the likelihood of renal adverse outcome (p = 0.034). CONCLUSIONS: The results of this propensity-based study show that the OPCAB technique may reduce the risk for minor and major renal adverse outcome after coronary artery bypass grafting.

Does minimally invasive vein harvesting technique affect the quality of the conduit for coronary revascularization?

The effect of minimally invasive great saphenous vein harvest on patient morbidity (wound infection and other healing disturbances) has been extensively investigated, yet its impact on the quality of the venous conduit is less well known. This study aims to review the literature with regard to macroscopic quality, postoperative myocardial infarction rates, and angiographic patency of the minimally invasive versus conventionally harvested vein using meta-analytic techniques where appropriate. Results suggest that conduits are comparable in macroscopic quality with minimally invasively harvested veins requiring more repairs prior to grafting. Postoperative myocardial infarction rates were not significantly different between groups, which is supported by the limited evidence on angiographic patency.

A new method of grafting the circumflex through lateral MIDCAB with the use of the radial loop technique.

We report a technique that allows total arterial revascularization of the circumflex territory without cardiopulmonary bypass through limited thoracotomy with the radial as a composite graft. The technique includes anastomosis of the distal end of the radial artery to its more proximal part after the division of the conduit from the brachial artery. In this way we create an adjustable loop that can be divided and used as bifurcated conduit in two coronary targets according to the needs of revascularization.

Relationship between connexins and atrial activation during human atrial fibrillation.

INTRODUCTION: Gap junctional connexin proteins (connexin40 [Cx40], connexin43 [Cx43]) are a determinant of myocardial conduction and are implicated in the development of atrial fibrillation (AF). We hypothesized that atrial activation pattern during AF is related to connexin expression and that this relationship is altered by AF-induced remodeling in the fibrillating atria of chronic AF. METHODS AND RESULTS: Isochronal activation mapping was performed during cardiac surgery on the right atria of patients in chronic AF (n = 13) using an epicardial electrode array. The atrial activation pattern was categorized using a complexity score based on the number of propagating wavefronts of activation and by grouping atria into those capable of uniform planar activation (simple) and those that were not (complex). The activation pattern was correlated with the levels of Cx43 and Cx40 signal measured by immunoconfocal quantification of biopsies from the mapped region. We studied the impact of electrical remodeling by comparing these findings with the unremodeled atria of patients in sinus rhythm during pacing-induced sustained AF (n = 17). In chronic AF, atria with complex activation had lower Cx40 signal than atria showing simple activation (0.013 +/- 0.006 microm(2)/microm(2) vs 0.027 +/- 0.009 microm(2)/microm(2), P < 0.02), with the relative connexin signal (Cx40/Cx40+Cx43) correlating with complexity score (P = 0.01, r =-0.74). This relationship did not occur in the unremodeled atria, and increased heterogeneity of distribution of Cx40 labeling in chronic AF was the only evidence of connexin remodeling that we detected in the overall group. CONCLUSION: The pattern of atrial activation is related to immunoconfocal connexin signal only in the fully remodeled atria of chronic AF. This suggests that intercellular coupling and pattern of atrial activation are interrelated, but only in conjunction with the remodeling of atrial electrophysiology that occurs in chronic AF.