Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

INTRODUCTION: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). METHODS: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). RESULTS: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. CONCLUSION: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Transseptal puncture in left atrial appendage closure guided by 3D printing and multiplanar CT reconstruction.

BACKGROUND: The presented study investigates the application of bi-arterial 3D printed models to guide transseptal puncture (TSP) in left atrial appendage closure (LAAC). AIMS: The objectives are to (1) test the feasibility of 3D printing (3DP) for TSP guidance, (2) analyse the distribution of the optimal TSP locations, and (3) define a CT-derived 2D parameter suitable for predicting the optimal TSP locations. METHODS: Preprocedural planning included multiplanar CT reconstruction, 3D segmentation, and 3DP. TSP was preprocedurally simulated in vitro at six defined sites. Based on the position of the sheath, TSP sites were classified as optimal, suboptimal, or nonoptimal. The aim was to target the TSP in the recommended position during the procedure. Procedure progress was assessed post hoc by the operator. RESULTS: Of 68 screened patients, 60 patients in five centers (mean age of 74.68 ± 7.64 years, 71.66% males) were prospectively analyzed (3DP failed in one case, and seven patients did not finally undergo the procedure). In 55 patients (91.66%), TSP was performed in the optimal location as recommended by the 3DP. The optimal locations for TSP were postero-inferior in 45.3%, mid-inferior in 45.3%, and antero-inferior in 37.7%, with a mean number of optimal segments of 1.34 ± 0.51 per patient. When the optimal TSP location was achieved, the procedure was considered difficult in only two (3.6%) patients (but in both due to complicated LAA anatomy). Comparing anterior versus posterior TSP in 2D CCT, two parameters differed significantly: (1) the angle supplementary to the LAA ostium and the interatrial septum angle (160.83° ± 9.42° vs. 146.49° ± 8.67°; p = 0.001), and (2) the angle between the LAA ostium and the mitral annulus (95.02° ± 3.73° vs. 107.38° ± 6.76°; p < 0.001), both in the sagittal plane. CONCLUSIONS: In vitro TSP simulation accurately determined the optimal TSP locations for LAAC and facilitated the procedure. More than one-third of the optimal TSP sites were anterior.

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.

Changes in cognitive function after thoracoscopic and catheter ablation for atrial fibrillation.

BACKGROUND: Comparative data regarding the effect of percutaneous and thoracoscopic ablation of atrial fibrillation (AF) on cognitive function are very limited. The aim of the study was to determine and compare the effect of both types of ablations on patient cognitive functions in the mid-term. METHODS: Patients with AF indicated for ablation procedure were included. Forty-six patients underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system, followed by a catheter ablation three months afterward (Hybrid group). A comparative cohort of 53 AF patients underwent pulmonary vein isolation only (PVI group). Neuropsychological examinations were done before and nine months after the surgical or catheter ablation procedure. Neuropsychological testing comprised 13 subtests of seven domains, and the results were expressed as post-operative cognitive dysfunction (POCD) nine months after the procedure. RESULTS: Patients in both groups were similar with respect to the baseline clinical characteristics; only non-paroxysmal AF was more common in the hybrid group (98% vs. 34%). Major POCD was present in eight (17.4%) of hybrid patients versus three (5.7%) of PVI patients (p = 0.11), combined (major/minor) worsened cognitive decline was present in 10 (21.7%) hybrid patients versus three (5.6%) PVI patients (p = 0.034). On the other hand, combined (major/minor) improvement was present in 15 (32.6%) hybrid patients versus nine (16.9%) patients in the PVI group (p = 0.099). CONCLUSION: Hybrid ablation, a combination of thoracoscopic and percutaneous ablation, is associated with a higher risk of cognitive decline compared to sole percutaneous ablation.

Left bundle branch area pacing results in more physiological ventricular activation than biventricular pacing in patients with left bundle branch block heart failure.

Biventricular pacing (Biv) and left bundle branch area pacing (LBBAP) are methods of cardiac resynchronization therapy (CRT). Currently, little is known about how they differ in terms of ventricular activation. This study compared ventricular activation patterns in left bundle branch block (LBBB) heart failure patients using an ultra-high-frequency electrocardiography (UHF-ECG). This was a retrospective analysis including 80 CRT patients from two centres. UHF-ECG data were obtained during LBBB, LBBAP, and Biv. Left bundle branch area pacing patients were divided into non-selective left bundle branch pacing (NSLBBP) or left ventricular septal pacing (LVSP) and into groups with V6 R-wave peak times (V6RWPT) < 90 ms and ≥ 90 ms. Calculated parameters were: e-DYS (time difference between the first and last activation in V1-V8 leads) and Vdmean (average of V1-V8 local depolarization durations). In LBBB patients (n = 80) indicated for CRT, spontaneous rhythms were compared with Biv (39) and LBBAP rhythms (64). Although both Biv and LBBAP significantly reduced QRS duration (QRSd) compared with LBBB (from 172 to 148 and 152 ms, respectively, both P < 0.001), the difference between them was not significant (P = 0.2). Left bundle branch area pacing led to shorter e-DYS (24 ms) than Biv (33 ms; P = 0.008) and shorter Vdmean (53 vs. 59 ms; P = 0.003). No differences in QRSd, e-DYS, or Vdmean were found between NSLBBP, LVSP, and LBBAP with paced V6RWPTs < 90 and ≥ 90 ms. Both Biv CRT and LBBAP significantly reduce ventricular dyssynchrony in CRT patients with LBBB. Left bundle branch area pacing is associated with more physiological ventricular activation.

The effect of left atrial appendage closure on heart failure biomarkers: A PRAGUE-17 trial subanalysis.

INTRODUCTION: The randomized PRAGUE-17 trial demonstrated noninferiority of left atrial appendage closure (LAAC) to non-vitamin K anticoagulants (NOACs) for the prevention of major cardiovascular or cerebrovascular events. However, the left atrial appendage is an important source of natriuretic peptides and plays a role in left atrial reservoir function. Changes of heart failure (HF) biomarkers after LAAC compared to NOAC has not been studied. The aim of the study was to compare the changes in concentrations of HF biomarkers between LAAC and NOAC patients. METHODS: Of 402 patients randomized in the PRAGUE-17 trial, biomarkers were analyzed in 144 patients (73 in the NOAC and 71 in the LAAC group). Both groups had similar baseline characteristics. Serum concentration of NT-proBNP, NT-proANP, Galectin-3, and GDF-15 were measured at baseline (before the procedure in the LAAC group), at the 6-month (and at 24-month for NT-proBNP) follow-up timepoint. RESULTS: There were no significant differences in baseline, 6 month, and delta (δ = baseline - 6 month) concentrations of NT-proANP between the groups (NOAC: baseline 2.6 [0.5; 4.9], 6-month 3.1 [1.8; 4.8], p = .068; LAAC: baseline 3.3 [1.1; 4.6], 6-month 2.6 [0.9; 5.3], p = .51; p value for δ in concentrations between groups = 0.42). Similarly, there were no significant differences in baseline, 6, 24 months, and delta concentrations of NT-proBNP between the groups (NOAC: baseline 461.0 [113.5; 1342.0], 6 month 440.0 [120.5; 1291.5], 24 month 798 [274; 2236], p = .39; LAAC: baseline 421.0 [100.0; 1320.0], 6 month 601.0 [145.0; 1230.0], 24 month 855 [410; 1367], p = .28; p value for δ in concentrations between groups = 0.73 at 6 months, and 0.58 at 24 months). Finally, no significant differences were present in baseline, 6 month, and δ concentrations of Galectin-3 and GDF-15 between the two groups. CONCLUSION: LAAC did not significantly influence the levels of HF biomarkers 6 months after the procedure.

Novel ultra-high-frequency electrocardiogram tool for the description of the ventricular depolarization pattern before and during cardiac resynchronization.

INTRODUCTION: The present study introduces a new ultra-high-frequency 14-lead electrocardiogram technique (UHF-ECG) for mapping ventricular depolarization patterns and calculation of novel dyssynchrony parameters that may improve the selection of patients and application of cardiac resynchronization therapy (CRT). METHODS: Components of the ECG in sixteen frequency bands within the 150 to 1000 Hz range were used to create ventricular depolarization maps. The maximum time difference between the UHF QRS complex centers of mass of leads V1 to V8 was defined as ventricular electrical dyssynchrony (e-DYS), and the duration at 50% of peak voltage amplitude in each lead was defined as the duration of local depolarization (Vd). Proof of principle measurements was performed in seven patients with left (left bundle branch block) and four patients with right bundle branch block (right bundle branch block) before and during CRT using biventricular and His-bundle pacing. RESULTS: The acquired activation maps reflect the activation sequence under the tested conditions. e-DYS decreased considerably more than QRS duration, during both biventricular pacing (-50% vs -8%) and His-bundle pacing (-77% vs -13%). While biventricular pacing slightly increased Vd, His-bundle pacing reduced Vd significantly (+11% vs -36%), indicating the contribution of the fast conduction system. Optimization of biventricular pacing by adjusting VV-interval showed a decrease of e-DYS from 102 to 36 ms with only a small Vd increase and QRS duration decrease. CONCLUSIONS: The UHF-ECG technique provides novel information about electrical activation of the ventricles from a standard ECG electrode setup, potentially improving the selection of patients for CRT and application of CRT.

Can QRS morphology be used to differentiate between true septal vs. apparently septal lead placement? An analysis of ECG of real mid-septal, apparent mid-septal, and apical pacing.

The location of the pacemaker lead is based on the shape of the lead on fluoroscopy only, typically in the left and right anterior oblique positions. However, these fluoroscopy criteria are insufficient and many leads apparently considered to be in septum are in fact anchored in anterior wall. Periprocedural ECG could determine the correct lead location. The aim of the current analysis is to characterize ECG criteria associated with a correct position of the right ventricular (RV) lead in the mid-septum. Patients with indications for a pacemaker had the RV lead implanted in the apex (Group A) or mid-septum using the standard fluoroscopic criteria. The exact position of the RV lead was verified using computed tomography. Based on the findings, the mid-septal group was divided into two subgroups: (i) true septum, i.e. lead was found in the mid-septum, and (ii) false septum, i.e. lead was in the adjacent areas (anterior wall, anteroseptal groove). Paced ECGs were acquired from all patients and multiple criteria were analysed. Paced ECGs from 106 patients were analysed (27 in A, 36 in true septum, and 43 in false septum group). Group A had a significantly wider QRS, more left-deviated axis and later transition zone compared with the true septum and false septum groups. There were no differences in presence of q in lead I, or notching in inferior or lateral leads between the three groups. QRS patterns of true septum and false septum groups were similar with only one exception of the transition zone. In the multivariate model, the only ECG parameters associated with correct lead placement in the septum was an earlier transition zone (odds ratio (OR) 2.53, P = 0.001). ECGs can be easily used to differentiate apical pacing from septal or septum-close pacing. The only ECG characteristic that could help to identify true septum lead position was the transition zone in the precordial leads. ClinicalTrials.gov identifier: NCT02412176.

Interventional left atrial appendage closure vs novel anticoagulation agents in patients with atrial fibrillation indicated for long-term anticoagulation (PRAGUE-17 study).

Atrial fibrillation (AF), with a prevalence of 1% to 2%, is the most common cardiac arrhythmia. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5% to 6%. The source of a cardioembolic event is a thrombus, which is usually formed in the left atrial appendage (LAA). Prevention of cardioembolic events involves treatment with anticoagulant drugs: either vitamin K antagonists or, recently, novel oral anticoagulants (NOAC). The other (nonpharmacologic) option for the prevention of a cardioembolic event involves interventional occlusion of the LAA. OBJECTIVE: To determine whether percutaneous LAA occlusion is noninferior to treatment with NOAC in AF patients indicated for long-term systemic anticoagulation. STUDY DESIGN: The trial will be a prospective, multicenter, randomized noninferiority trial comparing 2 treatment strategies in moderate to high-risk AF patients (ie, patients with history of significant bleeding, or history of cardiovascular event(s), or a with CHA2DS2VASc ≥3 and HAS-BLED score ≥2). Patients will be randomized into a percutaneous LAA occlusion (group A) or a NOAC treatment (group B) in a 1:1 ratio; the randomization was done using Web-based randomization software. A total of 396 study participants (198 patients in each group) will be enrolled in the study. The primary end point will be the occurrence of any of the following events within 24months after randomization: stroke or transient ischemic attack (any type), systemic cardioembolic event, clinically significant bleeding, cardiovascular death, or a significant periprocedural or device-related complications. CONCLUSION: The PRAGUE-17 trial will determine if LAA occlusion is noninferior to treatment with NOAC in moderate- to high-risk AF patients.

Periprocedural Intravascular Hemolysis During Atrial Fibrillation Ablation: A Comparison of Pulsed Field With Radiofrequency Ablation.

BACKGROUND: Hemolysis-related renal failure has been described after pulmonary vein isolation (PVI) with pulsed-field ablation (PFA). OBJECTIVES: This study sought to compare the potential for hemolysis during PVI with PFA vs radiofrequency ablation (RFA). METHODS: In consecutive patients, PVI was performed with PFA or RFA. Blood samples were drawn at baseline, immediately postablation, and 24 hours postablation. Using flow cytometry, the concentration of red blood cell microparticles (RBCµ) (fragments of damaged erythrocytes) in blood was assessed. Lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin were measured at baseline and 24 hours. RESULTS: Seventy patients (age: 64.7 ± 10.2 years; 47% women; 36 [51.4%] paroxysmal atrial fibrillation) were enrolled: 47 patients were in the PFA group (22 PVI-only and 36.4 ± 5.5 PFA applications; 25 PVI-plus, 67.3 ± 12.4 pulsed field energy applications), and 23 patients underwent RFA. Compared to baseline, the RBCµ concentration increased ∼12-fold postablation and returned to baseline by 24 hours in the PFA group (median: 70.8 [Q1-Q3: 51.8-102.5] vs 846.6 [Q1-Q3: 639.2-1,215.5] vs 59.3 [Q1-Q3: 42.9-86.5] RBCµ/µL, respectively; P < 0.001); this increase was greater with PVI-plus compared to PVI-only (P = 0.007). There was also a significant, albeit substantially smaller, periprocedural increase in RBCµ with RFA (77.7 [Q1-Q3: 39.2-92.0] vs 149.6 [Q1-Q3: 106.6-180.8] vs 89.0 [Q1-Q3: 61.2-123.4] RBCµ/µL, respectively; P < 0.001). At 24 hours with PFA, the concentration of LDH and indirect bilirubin increased, whereas haptoglobin decreased significantly (all P < 0.001). In contrast, with RFA, there were only smaller changes in LDH and haptoglobin concentrations (P = 0.03) and no change in bilirubin. CONCLUSIONS: PFA was associated with significant periprocedural hemolysis. With a number of 70 PFA lesions, the likelihood of significant renal injury is uncommon.

Myocardial Damage, Inflammation, Coagulation, and Platelet Activity During Catheter Ablation Using Radiofrequency and Pulsed-Field Energy.

BACKGROUND: Pulsed-field ablation (PFA) represents a new, nonthermal ablation energy for the ablation of atrial fibrillation (AF). Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation activation. OBJECTIVES: This study aimed to compare the systemic response in patients undergoing pulmonary vein isolation (PVI) using pulsed-field and radiofrequency (RF) energy. METHODS: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or pulsed-field (Farapulse, Boston-Scientific) energy. Markers of myocardial damage (troponin I), inflammation (interleukin-6), coagulation (D-dimers, fibrin monomers, von Willebrand antigen and factor activity), and platelet activation (P-selectin, activated GpIIb/IIIa antigen) were measured before the procedure (T1), after trans-septal puncture (T2), after completing the ablation in the left atrium (T3), and 1 day after the procedure (T4). RESULTS: A total of 65 patients were enrolled in the pulsed-field ablation (n = 33) and RF ablation (n = 32) groups. Both groups were similar in baseline characteristics (age 60.5 ± 12.7 years vs 64.0 ± 10.7 years; paroxysmal AF: 60.6% vs 62.5% patients). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09 ± 11:57 min vs 151:19 ± 41:25 min; P < 0.001; 36:00 ± 8:05 min vs 115:58 ± 36:49 min; P < 0.001). Peak troponin release was substantially higher in the PFA group (10,102 ng/L [IQR: 8,272-14,207 ng/L] vs 1,006 ng/L [IQR: 603-1,433ng/L]). Both procedures were associated with similar extents (>50%) of platelet and coagulation activation. The proinflammatory response 24 h after the procedure was slightly but nonsignificantly higher in the RF group. CONCLUSIONS: Despite 10 times more myocardial damage, pulsed-field ablation was associated with a similar degree of platelet/coagulation activation, and slightly lower inflammatory response. (The Effect of Pulsed-Field and Radiofrequency Ablation on Platelet, Coagulation and Inflammation; NCT05603637).

Deactivation of implantable cardioverter-defibrillators: results of patient surveys.

AIMS: The indications for implantable cardioverter-defibrillators (ICDs) have been expanding, especially for primary prevention of sudden cardiac death. Implantable cardioverter-defibrillator saves lives; however, in near end-of-life situations linked to incurable diseases, the question arises as to whether or not to turn off the ICD to avoid excessive numbers of shocks as the heart begins to fail. This study examined the wishes of a cohort of ICD recipients. METHODS AND RESULTS: Consecutive recipients of ICDs for primary or secondary prevention of sudden cardiac death were examined during a routine out-patient follow-up visit. Subjects completed a written survey about expected ICD benefits, feelings and circumstances under which they would want to deactivate the device. One hundred and nine patients fully completed the survey. Mean age was 67.6 ± 8.7 years, 91 (83.5%) were male and the mean systolic ejection fraction was 31.5 ± 10.9%. The severity of symptoms of heart failure according to the New York Heart Association classification was 2.1 ± 0.59 at implantation. Ninety-nine (90.8%) patients felt more secure and safe following ICD implantation and 66 (60.6%) patients reported a sense of improved health status after implantation. Thirty-one (28.4%) patients had experienced an ICD shock. Fifty (45.9%) patients indicated that they had never considered ICD deactivation during near end-of-life situations. This topic had been discussed with only eight (7.3%) patients. Forty-four (40.1%) patients wanted more information about ICD deactivation. On the other hand, 10 (41.7%) patients from secondary prevention and 19 (22.4%) from primary prevention groups categorically refused more information or further discussion on this topic (P = 0.058). CONCLUSION: Most ICD recipients felt safer following ICD implantation and most wanted more information regarding ICD deactivation. However, a significant number of patients (especially, secondary prevention patients) had no interest in receiving additional information about this topic.

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.

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.

Catheter ablation versus antiarrhythmic drugs with risk factor modification for treatment of atrial fibrillation: a protocol of a randomised controlled trial (PRAGUE-25 trial).

INTRODUCTION: Atrial fibrillation (AF), with a prevalence of 2%, is the most common cardiac arrhythmia. Catheter ablation (CA) has been documented to be superior to treatment by antiarrhythmic drugs (AADs) in terms of sinus rhythm maintenance. However, in obese patients, substantial weight loss was also associated with AF reduction. So far, no study has compared the modern non-invasive (AADs combined with risk factor modification (RFM)) approach with modern invasive (CA) treatment. The aim of the trial is to compare the efficacy of modern invasive (CA) and non-invasive (AADs with risk factor management) treatment of AF. METHODS AND ANALYSIS: The trial will be a prospective, multicentre, randomised non-inferiority trial. Patients with symptomatic AF and a body mass index >30 will be enrolled and randomised to the CA or RFM arm (RFM+AAD) in a 1:1 ratio. In the CA arm, pulmonary vein isolation (in combination with additional lesion sets in non-paroxysmal patients) will be performed. For patients in the RFM+AAD arm, the aim will be a 10% weight loss over 6-12 months, increased physical fitness and a reduction in alcohol consumption. The primary endpoint will be an episode of AF or regular atrial tachycardia lasting >30 s. The secondary endpoints include AF burden, clinical endpoints associated with AF reoccurrence, changes in the quality of life assessed using dedicated questionnaires, changes in cardiorespiratory fitness and metabolic endpoints. An AF freedom of 65% in the RFM+AAD and of 60% in the CA is expected; therefore, 202 patients will be enrolled to achieve the non-inferiority with 80% power, 5% one-sided alpha and a non-inferiority margin of 12%. ETHICS AND DISSEMINATION: The PRAGUE-25 trial will determine if modern non-invasive AF treatment strategies are non-inferior to CA. The study was approved by the Ethics Committee of the University Hospital Kralovske Vinohrady. Results of the study will be disseminated on scientific conferences and in peer-reviewed scientific journals. After the end of follow-up, data will be available upon request to principal investigator. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04011800).

4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation.

BACKGROUND: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk. OBJECTIVES: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17. METHODS: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA2DS2-VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat. RESULTS: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA2DS2-VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses. CONCLUSIONS: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944).

A Comparison of Cardiac Computed Tomography, Transesophageal and Intracardiac Echocardiography, and Fluoroscopy for Planning Left Atrial Appendage Closure.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) is accompanied by a high risk of complications. Due to the complex anatomy of the LAA and the oval-shaped ostium, the proper sizing of the device is often difficult. PURPOSE: To assess individualized fluoroscopy viewing angles using pre-procedural CT analysis and to compare the results of landing zone measurements obtained from CT, transesophageal echocardiography (TEE), intracardiac echocardiography (ICE), and fluoroscopy. METHODS: Patients with indications for LAAC were enrolled. Cardiac CT and TEE were done before the procedure; ICE and fluoroscopy measurements were done peri-procedurally. Multiplanar reconstruction of CT images, using FluoroCT software, was done, and optimal "personalized" viewing angles for fluoroscopy were determined. Moreover, a mean (using multiplanar CT reconstruction, derived from the LAA perimetr) amd maximum (using all four imaging modalitities) landing zone (LZ) of the LAA were masured. RESULTS: Twenty-five patients were analyzed. Despite significant correlation between LZs obtained from different imaging modalities, the values of LZs differed significantly; the mean LZ diameter on CT was 20.60 ± 3.42 mm, the maximum diameters were 21.99 ± 4.03 mm (CT), 18.72 ± 2.44 mm (TEE), 18.20 ± 2.68 mm (ICE), and 17.76 ± 3.24 mm (fluoroscopy). The mean CT diameter matched with the final device selection in 92% patients, while fluoroscopy or TEE maximum diameters in only 72% patients. Optimal viewing angles differed significantly from the fluoroscopy projections usually recommended by the manufacturer in 3 patients. CONCLUSIONS: CT provides the best measurement of the LZ and the best prediction of the optimum fluoroscopy projections for the implantation procedure.

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.

The Efficacy and Safety of Hybrid Ablations for Atrial Fibrillation.

OBJECTIVES: This study sought to comprehensively determine the procedural safety and midterm efficacy of hybrid ablations. BACKGROUND: Hybrid ablation of atrial fibrillation (AF) (thoracoscopic ablation followed by catheter ablation) has been used for patients with nonparoxysmal AF; however, accurate data regarding efficacy and safety are still limited. METHODS: Patients with nonparoxysmal AF underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system (Estech) followed by a catheter ablation 3 months afterward. The safety of the procedure was assessed using sequential brain magnetic resonance and neuropsychological examinations at baseline (1 day before), postoperatively (2-4 days for brain magnetic resonance imaging or 1 month for neuropsychological examination), and at 9 months after the surgical procedure. Implantable loop recorders were used to detect arrhythmia recurrence. Arrhythmia-free survival (the primary efficacy endpoint) was defined as no episodes of AF or atrial tachycardia while off antiarrhythmic drugs, redo ablations or cardioversions. RESULTS: Fifty-nine patients (age: 62.5 ± 10.5 years) were enrolled, 37 (62.7%) were men, and the mean follow-up was 30.3 ± 10.8 months. Thoracoscopic ablation was successfully performed in 55 (93.2%) patients. On baseline magnetic resonance imaging, chronic ischemic brain lesions were present in 60.0% of patients. New ischemic lesions on postoperative magnetic resonance imaging were present in 44.4%. Major postoperative cognitive dysfunction was present in 27.0% and 17.6% at 1 and 9 months postoperatively, respectively. The probability of arrhythmia-free survival was 54.0% (95% CI: 41.3-66.8) at 1 year and 43.8% (95% CI: 30.7-57.0) at 2 years. CONCLUSIONS: The thoracoscopic ablation is associated with a high risk of silent cerebral ischemia. The midterm efficacy of hybrid ablations is moderate.

Decreased apoptosis following successful ablation of atrial fibrillation.

OBJECTIVES: Increased apoptotic processes in tissue samples from hearts in atrial fibrillation (AF) have been previously documented in animals. Whether the restoration of sinus rhythm is associated with decreased apoptosis is not known. The aim of the present study was to establish whether successful epicardial ablation of AF leads to changes in the concentration of serum markers of apoptosis. METHODS: Twenty-five patients with AF were prospectively studied. All underwent epicardial isolation of pulmonary veins. The success of the ablation was assessed clinically and with 3 Holter recordings. Blood samples were drawn before surgery, and at 3 and 6 months after. Serum concentrations of Fas (apoptosis-stimulating fragment) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured using ELISA. RESULTS: AF was successfully ablated in 15 patients (SR group). In the other 10 patients (AF group), AF recurred during follow-up. Neither group differed with respect to age, sex, left ventricular ejection fraction, or preoperative concentrations of measured molecules. While Fas decreased in successfully ablated patients, there was no change in the Fas concentration in the AF group. Similarly, the concentrations of TRAIL decreased in the SR group, but remained unchanged in the AF group. CONCLUSION: The ablation of AF is associated with decreased serum markers for apoptosis.