Sequential hybrid ablation vs. surgical CryoMaze alone for treatment of atrial fibrillation: results of multicentre randomized controlled trial.

AIMS: Data on the hybrid atrial fibrillation (AF) treatment are lacking in patients with structural heart disease undergoing concomitant CryoMaze procedures. The aim was to assess whether the timely pre-emptive catheter ablation would achieve higher freedom from AF or atrial tachycardia (AT) and be associated with better clinical outcomes than surgical ablation alone. METHODS AND RESULTS: The trial investigated patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement with mandatory concomitant CryoMaze procedure who were randomly assigned to undergo either radiofrequency catheter ablation [Hybrid Group (HG)] or no further treatment (Surgery Group). The primary efficacy endpoint was the first recurrence of AF/AT without class I or III antiarrhythmic drugs as assessed by implantable cardiac monitors. The primary clinical endpoint was a composite of hospitalization for arrhythmia recurrence, worsening of heart failure, cardioembolic event, or major bleeding. We analysed 113 and 116 patients in the Hybrid and Surgery Groups, respectively, with a median follow-up of 715 (IQR: 528-1072) days. The primary efficacy endpoint was significantly reduced in the HG [41.1% vs. 67.4%, hazard ratio (HR) = 0.38, 95% confidence interval (CI): 0.26-0.57, P < 0.001] as well as the primary clinical endpoint (19.9% vs. 40.1%, HR = 0.51, 95% CI: 0.29-0.86, P = 0.012). The trial groups did not differ in all-cause mortality (10.6% vs. 8.6%, HR = 1.17, 95%CI: 0.51-2.71, P = 0.71). The major complications of catheter ablation were infrequent (1.9%). CONCLUSION: Pre-emptively performed catheter ablation after the CryoMaze procedure was safe and associated with higher freedom from AF/AT and improved clinical outcomes.

Prediction of post-operative atrial fibrillation in patients after cardiac surgery using heart rate variability.

PURPOSE: Post-operative atrial fibrillation (PoAF) occurs in ~ 30% of patients after cardiac surgery. The etiology of PoAF is complex, but a disbalance in autonomic systems plays an important role. The goal of this study was to assess whether pre-operative heart rate variability analysis can predict the risk of PoAF. METHODS: Patients without a history of AF with an indication for cardiac surgery were included. Two-hour ECG recordings one day before surgery was used for the HRV analysis. Univariate and multivariate logistic regression, including all HRV parameters, their combination, and clinical variables, were calculated to find the best predictive model for post-operative AF. RESULTS: One hundred and thirty-seven patients (33 women) were enrolled in the study. PoAF occurred in 48 patients (35%, AF group); the remaining 89 patients were in the NoAF group. AF patients were significantly older (69.1 ± 8.6 vs. 63.4 ± 10.5 yrs., p = 0.002), and had higher CHA2DS2-VASc score (3 ± 1.4 vs. 2.5 ± 1.3, p = 0.01). In the multivariate regression model, parameters independently associated with higher risk of AF were pNN50, TINN, absolute power VLF, LF and HF, total power, SD2, and the Porta index. A combination of clinical variables with HRV parameters in the ROC analysis achieved an AUC of 0.86, a sensitivity of 0.95, and a specificity of 0.57 and was more effective in PoAF prediction than a combination of clinical variables alone. CONCLUSION: A combination of several HRV parameters is helpful in predicting the risk of PoAF. Attenuation of heart rate variability increases the risk for PoAF.

Previous antithrombotic therapy does not have an impact on the in-hospital mortality of patients with upper gastrointestinal bleeding.

The association between antithrombotics (ATs) and the risk of gastrointestinal bleeding is well known; however, data regarding the influence of ATs on outcomes are scarce. The goals of this study are: (i) to assess the impact of prior AT therapy on in-hospital and 6-month outcomes and (ii) to determine the re-initiation rate of the ATs after a bleeding event. All patients with upper gastrointestinal bleeding (UGB) who underwent urgent gastroscopy in three centres from 1 January 2019 to 31 December 2019 were retrospectively analysed. Propensity score matching (PSM) was used. Among 333 patients [60% males, mean age 69.2 (±17.3) years], 44% were receiving ATs. In multivariate logistic regression, no association between AT treatment and worse in-hospital outcomes was observed. Development of haemorrhagic shock led to worse survival [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.2, P < 0.001; after PSM: OR 5.3, 95% CI 1.8-15.7, P = 0.003]. During 6-months follow-up, higher age (OR 1.0, 95% CI 1.0-1.1, P = 0.002), higher comorbidity (OR 1.4, 95% CI 1.2-1.7, P < 0.001), a history of cancer (OR 3.6, 95% CI 1.6-8.1, P < 0.001) and a history of liver cirrhosis (OR 2.2, 95% CI 1.0-4.4, P = 0.029) were associated with higher mortality. After a bleeding episode, ATs were adequately re-initiated in 73.8%. Previous AT therapy does not worsen in-hospital outcomes in after UGB. Development of haemorrhagic shock predicted poor prognosis. Higher 6-month mortality was observed in older patients, patients with more comorbidities, with liver cirrhosis and cancer.

Sequential hybrid ablation versus surgical CryoMaze alone for treatment of atrial fibrillation (SurHyb Trial): a protocol of the multicentre randomized controlled trial.

BACKGROUND: Atrial fibrillation is common in patients with structural heart disease who are undergoing cardiac surgery. Surgical CryoMaze has been shown to be an effective treatment in several trials, but success rates have varied considerably, between 47-95%. The sequential hybrid approach, combining surgical CryoMaze followed by radiofrequency catheter ablation, can achieve high freedom from atrial arrhythmias. However, in patients with concomitant surgical atrial fibrillation treatment, data comparing the hybrid approach to CryoMaze alone are lacking. METHODS: The SurHyb study was designed as a prospective, open-label, multicentre randomized trial. Patients with non-paroxysmal atrial fibrillation who were scheduled for coronary artery bypass grafting or valve repair/replacement were randomized to either surgical CryoMaze alone or surgical CryoMaze followed by radiofrequency catheter ablation 3 months post-surgery. The primary outcome measure was arrhythmia-free survival without class I or III antiarrhythmic drugs, which has been evaluated using implantable cardiac monitors. CONCLUSIONS: This is the first randomized study that compares concomitant surgical CryoMaze alone with the staged hybrid surgical CryoMaze followed by catheter ablation, in patients with non-paroxysmal atrial fibrillation using rigorous rhythm monitoring. The results may contribute to the optimization of the treatment in patients undergoing concomitant CryoMaze for atrial fibrillation.

A randomized comparison of HBP versus RVP: Effect on left ventricular function and biomarkers of collagen metabolism.

BACKGROUND: Right ventricular pacing (RVP) can result in pacing-induced cardiomyopathy (PICM). It is unknown whether specific biomarkers reflect differences between His bundle pacing (HBP) and RVP and predict a decrease in left ventricular function during RVP. AIMS: We aimed to compare the effect of HBP and RVP on the left ventricular ejection fraction (LVEF) and to study how they affect serum markers of collagen metabolism. METHODS: Ninety-two high-risk PICM patients were randomized to HBP or RVP groups. Their clinical characteristics, echocardiography, and serum levels of transforming growth factor ß1 (TGF-ß1), matrix metalloproteinase 9 (MMP-9), suppression of tumorigenicity 2 interleukin (ST2-IL), tissue inhibitor of metalloproteinase 1 (TIMP-1), and galectin 3 (Gal-3) were studied before pacemaker implantation and six months later. RESULTS: Fifty-three patients were randomized to the HBP group and 39 patients to the RVP group. HBP failed in 10 patients, who crossed over to the RVP group. Patients with RVP had significantly lower LVEF compared to HBP patients after six months of pacing (-5% and -4% in as-treated and intention-to-treat analysis, respectively). Levels of TGF-ß1 after 6 months were lower in HBP than RVP patients (mean difference -6 ng/ml; P = 0.009) and preimplant Gal-3 and ST2-IL levels were higher in RVP patients, with a decline in LVEF ≥5% compared to those with a decline of <5% (mean difference 3 ng/ml and 8 ng/ml; P = 0.02 for both groups). CONCLUSION: In high-risk PICM patients, HBP was superior to RVP in providing more physiological ventricular function, as reflected by higher LVEF and lower levels of TGF-ß1. In RVP patients, LVEF declined more in those with higher baseline Gal-3 and ST2-IL levels than in those with lower levels.

Acute efficacy of contiguous versus temporally discontiguous point-by-point radiofrequency pulmonary vein isolation in patients with paroxysmal atrial fibrillation: a randomized study.

PURPOSE: Durable pulmonary vein (PV) isolation (PVI) determines the clinical success of catheter ablation for atrial fibrillation. In this randomized study, we investigated whether the temporally discontiguous deployment of ablation lesions adversely affected the acute efficacy of PVI. METHODS: Thirty-six consecutive patients with drug-refractory paroxysmal atrial fibrillation (aged 59 ± 11, 58% males) were randomized 1:1 to either discontiguous (D-PVI) or contiguous (C-PVI) encircling radiofrequency (RF) lesions around ipsilateral PVs. A contact force-sensing catheter was used targeting a final interlesion distance < 6 mm and the ablation index of 400-450 (anterior wall) and 300-350 (posterior wall). The study endpoint was defined as failure of first-pass PVI or acute PV reconnection during a waiting time (> 30 min) followed by adenosine challenge. RESULTS: The total RF time, number of RF lesions, and mean interlesion distance were comparable in both groups. Total endpoint rates were 1/36 (3%) in the D-PVI vs 4/36 (11%) in the C-PVI groups; P = 0.34 for superiority, P = 0.008 for non-inferiority. Adenosine-induced reconnection of right PVs was the only endpoint in the D-PVI group. In the C-PVI group, first-pass PVI failed in 2 right PVs and spontaneous reconnection occurred in 2 other circles (left and right PVs). CONCLUSION: Temporally discontiguous deployment of RF lesions is not associated with lower procedural PVI efficacy when strict criteria for interlesion distance and ablation index are applied. The development of local edema around each ablation site does not prevent effective RF lesion formation at adjacent positions. TRIAL REGISTRATION: clinicaltrials.gov (NCT03332862).

Silent strokes after thoracoscopic epicardial ablation and catheter ablation for atrial fibrillation: not all lesions are permanent on follow-up magnetic resonance imaging.

BACKGROUND: Invasive treatments for atrial fibrillation (AF) pose a risk of ischemic stroke due to periprocedural brain embolization, which may be manifest or silent. The primary aim of our study was to compare the rate of silent strokes after percutaneous catheter-based and thoracoscopic epicardial ablation for AF. The secondary aim was to evaluate the development of silent strokes over time. METHODS: We included 39 subjects (aged 64.1±8.9 years) treated for persistent symptomatic AF with thoracoscopic ablation and 30 subjects (aged 64.1±10.5 years) treated for paroxysmal or persistent symptomatic AF with catheter ablation. Subjects underwent brain MRI before and early after the ablation, moreover, the surgical group underwent late MRI 6 months after therapy. On early MRI, the presence of silent strokes and their number and size were evaluated. On late MRI, transformation of previously-detected acute ischemic lesions into chronic infarction or their reversibility were assessed. RESULTS: Initially, different chronic ischemic findings were found in 64% of patients from the surgical group and in 70% from catheter group. Early MRI results: acute ischemic lesions were detected in 2 (6.7%) subjects (overall 3 lesions sized <5 mm) in the catheter group and in 17 (43.6%) subjects in surgical group. Most subjects in the surgical group showed multiple lesions (88%); 195 lesions were detected, a median 6 (IQR 8) lesions per case. Eighty-two percent of lesions were <5 mm, 12% 5-10 mm, 5% 10-30 mm, and 2% were large territorial ischemia. Only 1 case was symptomatic, the rest were silent strokes. On late MRI, 53.5% of all acute lesions were reversible. Lesions <5 mm were reversible in 63.1% of cases, lesions 5-10 mm were reversible in 21.7% and all lesions larger than 10 mm persisted. In 29.4% of patients all acute ischemic lesions were fully reversible. CONCLUSIONS: Periprocedural silent strokes were significantly more common after thoracoscopic epicardial ablation compared to catheter ablation considering both the number of affected patients and number of lesions. The majority of acute ischemic brain lesions were small, up to 5 mm in diameter, roughly half of which were reversible. Reversibility of acute ischemic lesions decreased with size. However, in 29.4% of affected patients, all lesions were fully reversible.

Improvement in the quality of life of patients with persistent or long-standing persistent atrial fibrillation after hybrid ablation.

BACKGROUND: Hybrid ablation (i.e., a combination of a thoracoscopic surgical ablation followed by a catheter ablation) is a treatment option for patients with non-paroxysmal atrial fibrillation (AF). Despite its promising efficacy, it is a surgical procedure with a relatively high risk of complications that could affect the quality of life (QoL) of patients, even when sinus rhythm is restored. OBJECTIVE: To describe changes in the QoL of patients with non-paroxysmal AF before and after a hybrid ablation. METHODS: Patients after hybrid ablation for persistent or long-standing persistent AF were prospectively studied. Follow-up visits were scheduled at 1, 3, 6, 9, and 12 months. The maintenance of SR was assessed using 1-week Holter recordings at 6 and 12 months and 24-h Holter recordings at 3 and 9 months, or via an implantable loop recorder. QoL was assessed using the Atrial Fibrillation Effect on Quality-of-life (AFEQT) and the EuroQoL-5Dimensions (EQ-5D) questionnaires before and 12 months after ablation. RESULTS: Seventy-five patients (49 men, age 62.9 ± 8.45 years, 48 (64%) with long-standing persistent AF) were enrolled. Fifty-two (69.3%, SR group) were AF-free during the 12-month follow-up, 16 (21.3%, PAROX group) had only paroxysms of AF after ablation, and 7 (9.3%, PERM group) were on rate control due to permanent AF reoccurrence. The AFEQT score increased significantly in the SR group from 59.9 ± 19.4 to 91.4 ± 10.8 (p < 0.001), and in the PAROX group from 58.8 ± 19.0 to 81.5 ± 14.1 (p = 0.002) but remained unchanged in the PERM group (44.6 ± 7.5 vs. 47.4 ± 5.5, p = 0.24). The EQ-5D score significantly decreased in the descriptive part (from 7.90 ± 2.61 to 6.64 ± 1.90, p = 0.0001) and increased on the visual analog scale (from 63.56 ± 19.11 to 79.30 ± 16.9, p < 0.0001) in the SR group. In the PAROX group, no significant change was present on either the descriptive part (p = 0.3) or in the visual analog scale (p = 0.48). Similarly, no significant changes were present on either the descriptive part (p = 0.93) or the visual analog scale (p = 0.4) in the PERM group. CONCLUSION: The QoL of patients with non-paroxysmal AF and patients with AF paroxysms, after successful hybrid ablation, improved significantly in patients with SR. No significant improvement was present in patients on rate control after an unsuccessful ablation.

Five-year outcomes in cardiac surgery patients with atrial fibrillation undergoing concomitant surgical ablation versus no ablation. The long-term follow-up of the PRAGUE-12 Study.

BACKGROUND: The long-term effect of concomitant surgical ablation (SA) on clinical outcomes in an unselected population of patients has not been sufficiently reported in randomized studies. OBJECTIVE: The aim of this study was to assess clinical outcomes of the SA after 5 years of follow-up. METHODS: The PRAGUE-12 study was a prospective, randomized clinical trial assessing cardiac surgery with ablation for AF vs cardiac surgery alone. Patients with AF who were also indicated for cardiac surgery (coronary artery disease [CAD], valve surgery) were randomized to SA or control (no ablation) group. All patients were followed for 5 years. The primary endpoint was a composite of cardiovascular death, stroke, hospitalization for heart failure, or severe bleeding. Secondary endpoint was a recurrence of AF. RESULTS: A total of 207 patients were analyzed (SA group = 108 patients, control group = 99 patients). Both groups were similar relative to important clinical characteristics except for CAD, which was more common in the control group. Cumulative incidence curves showed a higher incidence of the primary endpoint in the control group (P = .024, Gray's test). However, after adjusting for all covariables, the difference between groups was not significant (subhazard ratio [SHR] 0.69 [0.47-1.02], P = .068). The incidence of stroke and AF recurrences were significantly reduced in the SA group, and remained significant even after adjustment for all covariables, including CAD (stroke: SHR 0.32 [0.12-0.84], P = .02, AF recurrences: SHR 0.44 [0.31-0.62], P < .001). CONCLUSIONS: Concomitant SA of AF is associated with a greater likelihood of maintaining sinus rhythm and a decreased risk of stroke.

Residual echocardiographic and computed tomography findings after thoracoscopic occlusion of the left atrial appendage using the AtriClip PRO device.

OBJECTIVES: Thoracoscopic occlusion of the left atrial appendage (LAA) has become a routine part of thoracoscopic ablation for the treatment of atrial fibrillation (AF). Evaluation of residual findings of the occluded LAA by echocardiography has yet to be described. METHODS: Patients with AF indicated for hybrid ablation (thoracoscopic procedure followed by catheter ablation) were enrolled in this study. LAA was occluded as a routine part of the thoracoscopic procedure. Follow-up transoesophageal echocardiography was performed at the end of the procedure, 2-5 days and 2-3 months after the procedure (before the endocardial stage). The residual pouches of the LAA were measured in the mitral valve view (30-110°) and in the perpendicular view. The depth of the residual pouch was measured from the ostial plane (connecting the Coumadin ridge and the circumflex artery) to the deepest part of the residuum. The volume of the residual pouch and the distance from the circumflex artery to the proximal and the distal ends of the AtriClip were measured using computed tomography. RESULTS: Forty patients were enrolled in this study. The success rate for the occlusion of the LAA, assessed on transoesophageal echocardiography 2-5 days after surgery, was 97.5%. Regarding the residual findings, no reperfused LAAs were found, and only residual stumps remained. The depth of the stump was 12.9 ± 5.9 mm, the area was 2.2 ± 1.1 cm2, and the volume was 3.6 ± 1.9 ml (all data are shown as mean ± standard deviation). CONCLUSIONS: The occlusion of the LAA using an AtriClip PRO device was a clinically safe procedure with high efficacy and was associated with the presence of a small residual pouch after occlusion. Clinical trial registration: NCT02832206.

Two-staged hybrid ablation of non-paroxysmal atrial fibrillation: clinical outcomes and functional improvements after 1 year.

OBJECTIVES: Hybrid ablation of atrial fibrillation (AF) is a promising treatment strategy; however, data regarding its efficacy and safety are still limited. METHODS: Patients with non-paroxysmal AF were enrolled. First, a thoracoscopic, epicardial isolation of pulmonary veins and the left atrial posterior wall ('box lesion') was performed; a novel unipolar/bipolar radiofrequency device was used. Moreover, in 12 patients enrolled thereafter, the left atrial appendage was occluded. Electrophysiological evaluation and catheter ablation were performed 2-3 months later, with the goal of verifying or completing (if needed) the box lesion and ablation of the ganglionated plexi and the cavotricuspid isthmus. Outcomes were assessed using 1-week and 24-h Holter monitoring, repeated echocardiography and laboratory measurements. RESULTS: Thirty-eight patients (13 persistent and 25 long-standing persistent AF) were enrolled with a mean AF duration of 33 ± 32.9 months. The procedure was successfully completed in 35 patients; 3 patients underwent only the surgical part because of a postoperative left atrial appendage thrombus (2 patients) and perioperative stroke (1 patient). After 6 months, 30 (86%) patients were arrhythmia-free, whereas 80% were also off antiarrhythmics. After 1 year, 28 (82%) patients were arrhythmia-free, 79% were off anti-arrhythmics and 47% were off anticoagulation treatment. Four (10.5%) serious postoperative complications occurred, including 1 stroke, 1 right phrenic nerve palsy and 2 pneumothoraxes with a need for drainage. Significant improvements were observed in echocardiographic, functional and serological parameters. CONCLUSIONS: Hybrid ablation is an effective treatment strategy for patients with persistent or long-standing persistent AF. Over 80% of patients were arrhythmia-free 1 year after the procedure. Sinus rhythm restoration was accompanied by improvements in functional, echocardiographic and serological markers.

Risk of Intraatrial Thrombi After Thoracoscopic Ablation in Absence of Heparin and Appendage Closure.

BACKGROUND: Catheter and surgical ablation of atrial fibrillation (AF) can be associated with a risk of thromboembolic events. The goal of this study was to assess optimal anticoagulation management during thoracoscopic ablation of AF. METHODS: Fifty-two patients with persistent or long-standing persistent AF underwent hybrid ablation consisting of thoracoscopic ablation followed by electrophysiologic (EP) evaluation and consecutive ablation if indicated. The thoracoscopic ablation was performed using three different anticoagulation protocols: (1) without periprocedural heparin and without occlusion of the left atrial appendage; (2) with periprocedural heparin but without left atrial appendage occlusion; and (3) with periprocedural heparin and left atrial appendage occlusion. Transesophageal echocardiography (TEE) was obligatorily used to screen for intraatrial thrombi before the surgical and EP procedure and before hospital discharge for patients in protocols 2 and 3. RESULTS: In group 1 (n = 20), 1 patient (5%) had a postoperative stroke with persistent neurologic deficit, and 6 other patients (30%) had a new thrombus in the left atrial appendage seen on the pre-EP TEE. In group 2 (n = 6), 3 left atrial appendage thrombi occurred (50%; 2 on predischarge TEE and 1 on pre-EP TEE). In group 3 (n = 26), no intracardiac thrombi were found on predischarge and pre-EP TEE, and there were no strokes in this group of patients, namely, the rates of thrombus or stroke were significantly reduced when compared with groups 1 and 2 (p = 0.001). CONCLUSIONS: Thoracoscopic ablation of AF can be associated with a risk of left atrial appendage thrombus formation and possibly also stroke. With administration of heparin during the ablation, followed by occlusion of the left atrial appendage as a part of the procedure, this risk can be effectively reduced.

Treatment of stand-alone atrial fibrillation with a right thoracoscopic approach employing a microwave or monopolar radiofrequency energy source: long-term results.

OBJECTIVES: Minimally invasive surgery for atrial fibrillation (AF) has rapidly evolved recently. The long-term efficacy of most of these procedures is poorly known. METHODS: Between 2006 and 2010, 38 drug-resistant, symptomatic patients with stand-alone AF underwent unilateral, thoracoscopic, off-pump ablation. The mean age was 60 ± 8.2 (range 42-75) years and the mean AF duration was 46 ± 62 (range 3-240) months. Sixteen patients (42%) had paroxysmal, 9 (24%) had persistent and 13 (34%) had long-standing persistent AF. A box lesion was created using a microwave (26 patients) or monopolar radiofrequency (12 patients) system. Patients were prospectively followed with repeat electrocardiograms (ECGs) and ECG Holters. Additional catheter ablation was offered to patients with recurrence of arrhythmia. RESULTS: All procedures were completed as planned with one conversion to sternotomy, zero mortality and minimal in-hospital complications. The mean follow-up duration was 70 ± 19 (range 20-88) months. Arrhythmia-free survival rates after the procedure were 50, 44.4, 24.1 and 10.8% at 6, 12, 36 and 60 months, respectively, with most recurrences in the first 6 months. Twelve patients underwent additional catheter ablation(s); from the last intervention, 75% of them were in sinus rhythm (SR) with a mean follow-up of 31 ± 23 (range 4-86) months. Overall, at the end of follow-up, only 3 patients were still in SR without any arrhythmia recurrence. Major complications (cerebral, peripheral embolism or bleeding) occurred in 5 patients. CONCLUSIONS: Unilateral, thoracoscopic AF ablation is safe and technically feasible. However, the results of the microwave and monopolar radiofrequency devices were less than satisfactory, with a gradual decline in arrhythmia-free survival over a very long-term follow-up.

Electrophysiological findings after surgical thoracoscopic atrial fibrillation ablation.

BACKGROUND: Hybrid ablation (a combination of thoracoscopic epicardial ablation and catheter ablation) has become a new technique for atrial fibrillation treatment. OBJECTIVE: The goal of this study was to evaluate the success and electrophysiological follow-up after using the COBRA Fusion device to deliver a circumferential lesion set anterior to the pulmonary veins in an attempt to isolate the posterior left atrium (box isolation). METHODS: Surgical ablation was carried out via a thoracoscopic approach using the COBRA Fusion radiofrequency catheter. An electrophysiology study was done 2-3 months later to verify box isolation (and to complete it, if needed) and to perform right-sided isthmus ablation. Fat thickness along the presumed box lesion line was measured using preprocedural computed tomography. RESULTS: Thirty patients (mean age 60.0 ± 11.6 years; 22 men; 8 with long-standing persistent AF and 22 with persistent atrial fibrillation) were enrolled. The duration of the EP study was 216.3 ± 64.2 minutes. Box isolation, based on the EP study, was complete in 12 patients (40%) and incomplete in 18 patients (60%). Successful box isolation was achieved with catheter ablation in 16 of 18 patients (89%). A total of 39 gaps in these 16 patients were identified. Typical gap locations were the anterior-superior part of the superior pulmonary veins and the roofline. Fat thickness along the roofline was substantially higher than that along the inferior line (4.58 ± 1.61 mm vs 2.37 ± 0.76 mm; P < .001). CONCLUSION: There is a relatively low rate of complete isolation using the COBRA catheter ablation system. The superior line and anterior parts of superior pulmonary veins have most conduction gaps.

Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

Predictors of complete arrhythmia free survival in patients undergoing surgical ablation for atrial fibrillation. PRAGUE-12 randomized study sub-analysis.

BACKGROUND: Surgical ablation (SA) is commonly used in atrial fibrillation (AF) patients undergoing cardiac surgery. However, its effect has been established in few randomized studies. To assess the complete atrial fibrillation free (AF-free) survival in randomized study assessing the effects of additional concomitant SA of AF in patients primarily indicated for other cardiac surgery. METHODS: The PRAGUE-12 study was a prospective randomized study comparing the effect of adding SA to other cardiac surgery. We examined the data from the PRAGUE-12 trial and grouped patients according to complete AF-free survival. All patients had regular check-ups at 3, 6, 9 months, some of them with Holter recordings, and a final check-up at 12 months with Holter recording. RESULTS: One hundred ninety-four patients were analyzed; 104 originally randomized to surgery with adding SA (SA group) and 90 without it (non-SA group). Complete AF-free status was found in 46 patients from the SA group (44.2%) and 25 patients (27.8%) from the non-SA group (p<0.05). In a multivariate logistic regression, the SA group was associated with a greater chance for complete AF-free survival (OR 1.87, p<0.05). In the multivariate analysis of the SA group, history of myocardial infarction (OR 0.2, p<0.05) and a higher EuroSCORE (OR 0.9, p 0.05) were independently associated with a lower probability of AF-free survival. CONCLUSION: Complete AF-free survival following SA was present in almost one half of patients. Patients with a history of myocardial infarction and higher EuroSCOREs were less likely to benefit from an add-on SA procedure.

Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy.

OBJECTIVES: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-ß cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. METHODS: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-α, TNF-receptor 1, TGF-ß1 and interleukin (IL)-6 were measured using ELISA. RESULTS: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-α and TGF-ß1 decreased significantly. In nonresponders, the concentration of TGF-ß1 even increased significantly. In multivariate analysis, the concentration of TGF-ß1 was a significant predictor of death during follow-up. CONCLUSIONS: The response to CRT implantation was associated with a decrease of TGF-ß1, IL-6 and TNF-α. Higher pre-implant concentrations of TGF-1ß were independently associated with a poor prognosis in CRT patients.

Prognostic value of TNF-related apoptosis inducing ligand (TRAIL) in acute coronary syndrome patients.

BACKGROUND: Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes. METHODS: The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone. RESULTS: During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03-0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1-54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05-0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004-0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02-1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56-145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters. CONCLUSIONS: Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.

Design and rationale of the PRAGUE-12 trial: a large, prospective, randomized, multicenter trial that compares cardiac surgery with left atrial surgical ablation with cardiac surgery without ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation.

Surgical ablation procedure can restore sinus rhythm (SR) in patients with atrial fibrillation (AF) undergoing cardiac surgery. However, it is not known whether it has any impact on clinical outcomes. There is a need for a randomized trial with long-term follow-up to study the outcome of surgical ablation in patients with coronary and/or valve disease and AF. Patients are prospectively enrolled and randomized either to group A (cardiac surgery with left atrial ablation) or group B (cardiac surgery alone). The primary efficacy outcome is the SR presence (without any AF episode) during a 24-hour electrocardiogram after 1 year. The primary safety outcome is the combined end point of death, myocardial infarction, stroke, and renal failure at 30 days. Long-term outcomes are a composite of total mortality, stroke, bleeding, and heart failure at 1 and 5 years. We finished the enrollment with a total of 224 patients from 3 centers in 2 countries in December 2011. Currently, the incomplete 1-year data are available, and the patients who enrolled first will have their 5-year visits shortly. PRAGUE-12 is the largest study to be conducted so far comparing cardiac surgery with surgical ablation of AF to cardiac surgery without ablation in an unselected population of patients who are operated on for coronary and/or valve disease. Its long-term results will lead to a better recognition of ablation's potential clinical benefits.

Comparison of cardiac surgery with left atrial surgical ablation vs. cardiac surgery without atrial ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation: final results of the PRAGUE-12 randomized multicentre study.

AIMS: Surgical ablation procedure can restore sinus rhythm (SR) in patients with atrial fibrillation (AF) undergoing cardiac surgery. However, it is not known whether it has any impact on long-term clinical outcomes. METHODS AND RESULTS: This multicentre study randomized 224 patients with AF scheduled for valve and/or coronary surgery: group A (left atrial surgical ablation, n = 117) vs. group B (no ablation, n = 107). The primary efficacy outcome was the SR presence (without any AF episode) during a 24 h electrocardiogram (ECG) after 1 year. The primary safety outcome was the combined endpoint of death/myocardial infarction/stroke/renal failure at 30 days. A Holter-ECG after 1 year revealed SR in 60.2% of group A patients vs. 35.5% in group B (P = 0.002). The combined safety endpoint at 30 days occurred in 10.3% (group A) vs. 14.7% (group B, P = 0.411). All-cause 1-year mortality was 16.2% (A) vs. 17.4% (B, P = 0.800). Stroke occurred in 2.7% (A) vs. 4.3% (B) patients (P = 0.319). No difference (A vs. B) in SR was found among patients with paroxysmal (61.9 vs. 58.3%) or persistent (72 vs. 50%) AF, but ablation significantly increased SR prevalence in patients with longstanding persistent AF (53.2 vs. 13.9%, P < 0.001). CONCLUSION: Surgical ablation improves the likelihood of SR presence post-operatively without increasing peri-operative complications. However, the higher prevalence of SR did not translate to improved clinical outcomes at 1 year. Further follow-ups (e.g. 5-year) are warranted to show any potential clinical benefit which might occur later.