Long-term success of a multi-electrode substrate mapping and ablation strategy versus a classic single tip mapping and ablation strategy for ventricular tachycardia ablation in patients with ischemic cardiomyopathy.

INTRODUCTION: Over the past years, mapping and ablation techniques for the treatment of ventricular tachycardia (VT) have evolved rapidly. High Density (HD) substrate mapping is now routine and pre-procedural imaging is increasingly used. The additional value of these techniques for long-term VT-free survival is not clear. METHODS: We compared baseline and procedural characteristics, procedural success, safety and outcome of mapping and ablation of ventricular tachycardia in patients with ischemic heart disease between two groups. (1) Low Density (LD) group: VT mapping and ablation with a 4 mm single tip catheter (2) HD group: HD substrate mapping with the Pentaray (Biosense Webster, USA) or HD Grid (Abbott, USA) catheter and ablation with a 4 mm single tip catheter. RESULTS: VT ablation was performed in 133 patients (71 patients in LD group and 62 patients in HD group). The median follow-up was 5.0 years in LD group and 2.0 years in HD group. One-, two-, and five-year VT recurrence rates were 47%, 56%, and 65% in the LD group versus 39%, 50%, and 55% in the HD group (log-rank test for VT recurrence p = .70). One-, two-, and five-year ICD shock recurrence rates were 14%, 18%, and 24% in the LD group versus 8%, 15%, and 19% in the HD group (log-rank test for ICD-shock p = .79). All-cause mortality, cardiac (non-arrhythmic), and arrhythmic death, were similar in both groups. Severe procedural complications (tamponade, stroke, or procedural death) occurred in four patients (5%, 1 vascular, 3 tamponade) in the LD group versus two patients (3%, both tamponade) in the HD group (NS). In univariate and multivariable analysis, only a higher LVEF was significantly associated with VT-free survival. HD mapping was not significantly associated with VT-free survival. Anterior infarct location and age were significantly associated with ICD recurrent shock in both univariate and multivariable analyses. CONCLUSIONS: In patients with ischemic cardiomyopathy, a HD substrate mapping, and ablation strategy did not lead to higher VT-free survival and shock-free survival compared to a single tip mapping and ablation strategy. In this study, only LVF is an independent predictor for VT recurrence. Anterior infarct location and age predict recurrent ICD shocks.

High-density mapping for ablation of atypical atrial flutters - procedural characteristics related to outcome.

BACKGROUND: High-density (HD) mapping is increasingly used to characterize arrhythmic substrate for ablation of atypical atrial flutters (AAFl). However, results on clinical outcomes and factors that are associated with arrhythmia recurrence are scarce. METHODS: Single-center, prospective, observational cohort study that enrolled patients with catheter ablation for AAFl using a HD mapping system and a grid-shaped mapping catheter. Procedural characteristics, rates of atrial flutter recurrence, and factors that were associated with atrial flutter recurrence were evaluated. RESULTS: Sixty-one patients with a total of 94 AAFl were included in the cohort. HD mapping was used to successfully identify the flutter circuit of 80/94 AAFl. The circuit was not identified for 14/94 AAFl in 11 patients. Critical isthmuses were identified and ablated in 29 patients (48%). Acute procedural success was achieved in 52 patients (85%), and 37 patients (61%) remained free from atrial flutter recurrence during a follow up of 1.3 [1.0-2.1] years. Atrial flutter recurrence was univariably associated with presence of a non-identified flutter circuit (HR:2.6 95% CI [1.1-6.3], p = .04) and critical isthmus-targeted ablation (HR:0.4 [0.15-0.90], p = .03). In multivariable regression analyses, critical isthmus ablation remained significant (HR:0.4 [0.16-0.97], p = .04), whereas presence of a non-identified flutter did not (HR:2.4 [0.96-5.8], p = .06). CONCLUSION: HD mapping was successfully used to identify the majority of AAFl circuits. Ablation resulted in freedom from atrial flutter recurrence in 61% of the cohort. Successful identification of all flutter circuits and critical isthmuses appears to be beneficial for long-term outcomes.

Dielectric imaging for electrophysiology procedures: The technology, current state, and future potential.

Electroanatomic mapping systems have become an essential tool to guide the identification and ablation of arrhythmic substrate. Recently, a novel guiding system for electrophysiology procedures was introduced that uses dielectric sensing to perform high resolution anatomical imaging. Dielectric imaging systems use electrical fields to differentiate anatomic structures based on their conductivity and permittivity. This technique enables non-fluoroscopic, noncontact mapping of anatomic structures, assessment of pulmonary vein occlusion state during cryoballoon ablation, and has the potential to assess for additional tissue characterization including tissue thickness and tissue type. This article elaborates on the functioning and potential of dielectric imaging systems and provides two cases to illustrate the clinical impact for electrophysiology procedures.

Efficacy and safety of the GOLD FORCE multicentre randomized clinical trial: multielectrode phased radiofrequency vs. irrigated radiofrequency single-tip catheter with contact force ablation for treatment of symptomatic paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) for atrial fibrillation (AF) has become increasingly safe and effective with the evolution of single-tip ablation catheters aided by contact force sensing (ST-CF) and single-shot devices such as the second-generation pulmonary vein ablation catheter (PVAC) Gold multi-electrode array. The multicentre randomized GOLD FORCE trial was conducted to evaluate non-inferiority of safety and efficacy of PVAC Gold PVI compared to ST-CF ablation for paroxysmal AF. METHODS AND RESULTS: The primary efficacy endpoint documented AF recurrence ≥30 s was assessed by time-to-first-event analysis after a 90-day blanking period using repeated 7-day Holters. Secondary endpoints include acute success and procedural characteristics. Safety endpoints included procedural complications, stroke/transient ischaemic attack (TIA), tamponade, bleeding, and access site complications. Two hundred and eight patients underwent randomization and PVI (103 assigned to PVAC Gold, 105 to ST-CF). Acute success rates were 95% and 97% for PVAC Gold and ST-CF, respectively. At 12 months, AF recurrence was observed in 46.6% of the PVAC Gold group and in 26.2% of the ST-CF group [absolute efficacy difference 20.4% (95% confidence interval, CI 7.5-33.2%), hazard ratio 2.05 (95% CI 1.28-3.29), P = 0.003]. PVAC Gold had significantly shorter procedure and ablation times. Complication rates were 5.7% and 4.9% for PVAC Gold and ST-CF, respectively (P = 0.782). CONCLUSION: In this multicentre randomized clinical trial, ablation with ST-CF and PVAC Gold ablation catheters non-inferiority for efficacy was not met. AF recurrence was significantly more frequent in the PVAC Gold group compared to single-tip contact force group. Both groups had similarly low rates of adverse events. PVAC Gold ablation had significantly shorter procedure and ablation times.

ICD implantation for secondary prevention in patients with ventricular arrhythmia in the setting of acute cardiac ischemia and a history of myocardial infarction.

INTRODUCTION: In patients with a prior myocardial infarction (MI) but preserved left ventricular (LV) function, sustained ventricular arrhythmias (VAs) may arise in the setting of an acute coronary syndrome (ACS). It is unknown whether an implantable cardioverter-defibrillator (ICD) is mandatory in these patients as VA might be triggered by a reversible cause. The purpose of this study is to analyze the benefit of ICD therapy in this patient population. METHODS: We conducted a retrospective observational study in ICD recipients implanted from 2008 to 2011. The study group consisted of patients with sustained VA in the setting of an ACS, with a history of MI, but with left ventricular ejection fraction (LVEF) greater than 35 (group A). The two control groups consisted of patients admitted with VA with a history of MI, but without ACS at presentation, either with LVEF greater than 35% (group B) or ≤35% (group C). The primary endpoint was the number of patients with appropriate ICD therapy (antitachycardia pacing or shock). RESULTS: A total of 291 patients were included with a mean follow-up of 5.3 years. Appropriate ICD therapy occurred in 45.6% of the patients in group A vs 51.6% and 60.4% in groups B and C (P = .11). In group A, 31.1% received an appropriate ICD shock vs 34.7% and 44.3% in control groups B and C (P = .12). CONCLUSION: On the basis of these data, ICD implantation seems warranted in patients with history of MI presenting with VA in the setting of an ACS, despite preserved LV function and adequate revascularization. Further trials, preferably randomizes, should be performed to address these findings.

Left atrial catheter ablation in patients with previously implanted left atrial appendage closure devices.

AIMS: Left atrial appendage closure (LAAC) is increasingly used as an alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) patients. Feasibility and safety of left atrial (LA) catheter ablation (CA) in patients with previously implanted LAAC devices have not been well studied. We report on the feasibility, safety, and efficacy of LA CA in the presence of a previously implanted LAAC device. METHODS AND RESULTS: In this prospective cohort study consecutive patients that underwent LA CA with a previously implanted Watchman device were included. Periprocedural characteristics and long-term clinical follow-up were evaluated. Twenty-three LA CA procedures were performed in 19/162 AF patients with previously implanted Watchman devices [47% male, age 63.9 ± 6.2 years, CHA2DS2-VASc 4.0 (3.0-5.0); HASBLED 3.0 (2.0-4.0); 63% paroxysmal]. Left atrial CA was performed with irrigated radiofrequency (RF; n = 20, 87%) or phased RF (n = 3, 13%) in a mean of 18 months after LAAC implantation (range 4-80 months). Targets of CA consisted of pulmonary vein isolation (n = 19, 83%), superior vena cava isolation (n = 13, 57%), and additional linear lesions (n = 8, 35%). Procedures were carried out under vitamin K antagonist (VKA; n = 6, 26%), non-VKA OAC (NOAC; n = 8, 35%), or single antiplatelet therapy alone (n = 9, 39%). Left atrial CA was successful without any signs of interference from the device. Procedure-related complications were not observed. During a mean follow-up of 28 months, 11 patients (58%) had AF recurrence. CONCLUSION: Left atrial CA after LAAC appears to be feasible, effective, and safe in this single centre cohort. Previously implanted Watchman device should not be a reason to relinquish CA in symptomatic AF patients, even in patients on single antiplatelet therapy alone.

Effects of epicardial versus transvenous left ventricular lead placement on left ventricular function and cardiac perfusion in cardiac resynchronization therapy: A randomized clinical trial.

INTRODUCTION: Optimal left ventricular (LV) lead position in patients undergoing cardiac resynchronization therapy (CRT) is crucial to achieve an optimal effect on hemodynamics. Due to various difficulties, up to 30% of transvenous LV lead placements fail, or a suboptimal position is achieved. Surgical epicardial LV lead placement could be performed at a position anticipated to be the optimal site. This could have a more favorable effect, which may be expressed by increased improvement in left ventricular ejection fraction (LVEF) and cardiac perfusion. The objective of this trial is to compare transvenous versus epicardial LV lead placement in CRT in a randomized fashion METHODS AND RESULTS: Fifty-two patients were randomized to either epicardial or transvenous approach. All patients received an ICD with CRT. Patients were followed for 6 months after device implant. Primary endpoint was the degree of change in cardiac perfusion measured by myocardial perfusion scintigraphy. LVEF equally improved in both groups, from 24% to 36% in the transvenous group versus 25% to 35% in the epicardial group (P = 0.797). Cardiac perfusion, expressed as summed stress score, improved in both groups without a significant difference as well (P = 0.727). Complication rate was similar, respectively 6 and 7 patients had any complication. Admission time was significantly longer in the epicardial group with 2 (2-7) versus 3 (2-32) days (P <0.001). CONCLUSION: Epicardial LV lead placement does not result in additional improvement of LVF or myocardial perfusion compared to the conventional transvenous in CRT.

Different impact of long-detection interval and anti-tachycardia pacing in reducing unnecessary shocks: data from the ADVANCE III trial.

AIMS: A long-detection interval (LDI) (30/40 intervals) has been proved to be superior to a standard-detection interval (SDI) (18/24 intervals) in terms of reducing unnecessary implantable cardioverter defibrillator (ICD) therapies. To better evaluate the different impact of LDI and anti-tachycardia pacing (ATP) on reducing painful shocks, we assessed all treated episodes in the ADVANCE III trial. METHODS AND RESULTS: A total of 452 fast (200 ms < cycle length ≤ 320 ms) arrhythmic episodes were recorded: 284 in 138 patients in the SDI arm and 168 in 82 patients in the LDI arm (106/452 inappropriate detections). A total of 346 fast ventricular tachycardias (FVT) were detected in 169 patients: 208 in 105 patients with SDI and 138 in 64 patients with LDI. Setting LDI determined a significant reduction in appropriate but unnecessary therapies [208 in SDI vs. 138 in LDI; incidence rate ratio (IRR): 0.61 (95% CI 0.45-0.83), P = 0.002]. Anti-tachycardia pacing determined another 52% reduction in unnecessary shocks [208 in SDI with hypothetical shock-only programming vs. 66 in LDI with ATP; IRR: 0.37 (95% CI 0.25-0.53, P < 0.001)]. The efficacy of ATP in terminating FVT was 63% in SDI and 52% in LDI (P = 0.022). No difference in the safety profile (acceleration/degeneration and death/cardiovascular hospitalizations) was observed between the two groups. CONCLUSION: The combination of LDI and ATP during charging is extremely effective and significantly reduces appropriate but unnecessary therapies. The use of LDI alone yielded a 39% reduction in appropriate but unnecessary therapies; ATP on top of LDI determined another 52% reduction in unnecessary shocks. The strategy of associating ATP and LDI could be considered in the majority of ICD recipients.

Efficacy of long detection interval implantable cardioverter-defibrillator settings in secondary prevention population: data from the Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) trial.

BACKGROUND: Three trials demonstrated recently that a long detection window reduces implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) was the only trial that enrolled both primary and secondary prevention patients. METHODS AND RESULTS: Of the 1902 patients enrolled in the ADVANCE III trial, 477 received a defibrillator for secondary prevention; 248 patients were randomly assigned to a long detection setting (30 of 40 intervals) and 229 to the nominal setting (18 of 24 intervals) for ventricular arrhythmias with cycle length ≤ 320 ms. Eight-five percent of patients were men, with a mean age of 65 ± 12 years, a previous history of ventricular fibrillation in 37% of the cases, and a mean ejection fraction of 38 ± 13%. The ICD device mix was 37% single chamber, 47% dual chamber, and 16% triple chamber. Over a median period of 12 months, the long detection period was associated with a 25% reduction in the number of overall therapies (115.6 versus 86.8 per 100 patient-years; incidence rate ratio, 0.75; 95% confidence interval, 0.61-0.93; P=0.008) and a 34% reduction in the number of shocks (rate per 100 patient-years, 51.2 versus 38.1; incidence rate ratio, 0.66; 95% confidence interval, 0.48-0.89; P=0.007). Appropriate therapies (89.7 versus 67.7; incidence rate ratio, 0.77; 95% confidence interval, 0.60-0.97; P=0.029) and appropriate shocks (37.1 versus 28.1; incidence rate ratio, 0.64; 95% confidence interval, 0.45-0.93; P=0.018) were also reduced. CONCLUSIONS: ADVANCE III is the first randomized trial to assess a long detection window setting in ICDs in both primary and secondary prevention populations and demonstrates a reduction of overall therapies and shocks in the subgroup of secondary prevention patients. These data suggest that even the secondary prevention population may benefit from programming that combines a long detection period with antitachycardia pacing during charging. CLINICAL TRIAL REGISTRATION URL: http://www/clinicaltrials.gov. Unique identifier: NCT00617175.

Dielectric response as a novel marker for ablation lesion quality: Relation to conventional ablation parameters.

Background: The tissue response viewer (TRV) is a novel marker for ablation lesion quality that aims to classify lesions into transmural or nontransmural lesions (high or low dielectric response, HDR or LDR) using dielectric-based tissue assessment. The objective of this study was to gain insight in the TRV by relating its outcomes to conventional ablation parameters. Methods: Patients that had repeat ablation for atrial fibrillation with a dielectric imaging-based mapping system were enrolled. All ablation data were downloaded from the mapping system and analyzed to explore associations between TRV outcomes and other ablation parameters. Results: The cohort included 24 patients, in which 58 pulmonary veins and 8 superior vena cavas were targeted. A total of 388 energy applications were applied, resulting in 639 ablation points. The system classified 36% of ablation points as HDR and 44% as LDR. The system did not provide a dielectric response in 20%. The system's ability to provide a dielectric response was related to longer ablation duration and absence of dragging ablation. HDR (versus LDR) was multivariably associated with longer energy applications, higher mean ablation power, and lower wall thickness. Greater impedance drop was univariably associated with HDR. Conclusion: Outcomes of the TRV are associated with conventional ablation parameters (e.g., duration and power) but also local wall thickness. Catheter stability seems important for successful lesion assessment with the TRV. Further reduction of missing outcomes and validation of the tool are warranted before widespread use.

Freedom from paroxysmal atrial fibrillation after successful pulmonary vein isolation with pulmonary vein ablation catheter-phased radiofrequency energy: 2-year follow-up and predictors of failure.

AIMS: In patients with paroxysmal atrial fibrillation (PAF) the pattern of atrial fibrillation (AF) episodes and the total AF burden, may be related to the efficacy of pulmonary vein isolation (PVI). We evaluated (pre)-procedural factors explaining the long-term outcome after PVI, using a ring-shaped multielectrode ablation catheter [pulmonary vein ablation catheter (PVAC)]. METHODS AND RESULTS: A total of 120 consecutive patients with PAF were treated with the PVAC. The patients' histories were obtained by a questionnaire and the clinical charts. Follow-up was performed at 3, 6, 12, 18, and 24 months with serial electrocardiogram, and multiple day Holter at 6, 12, and 24 months, as well as event recording in case of unexplained palpitations. At 1 year, 66 of 120 (55%, 95% confidence interval (CI) [46-63%]) patients were free of any left atrial (LA) arrhythmia without class I or III anti-arrhythmics after a single procedure. At 2 years, freedom from LA arrhythmia slightly declined further to 58 of 119 (49%, 95% CI [40-58%]). The only pre-procedural predictor of long-term success was a shorter duration of the longest episode of AF (hazard ratio (HR) 0.77 95% CI [0.64-0.92]). The only procedural predictor of long-term success was no need for direct current cardioversion (DCCV) for AF (HR 0.36 95% CI [0.21-0.61]). Since other characteristics in these PAF patients were very homogeneous, no further clinical predictors were observed. CONCLUSION: Freedom from LA arrhythmia after PVI for PAF with PVAC is 49% after 2-year follow-up, with little decline between year 1 and 2. Predictors of long-term failure were a longer duration of the longest episode of AF in the pre-procedural questionnaire, and a procedural DCCV for AF.

Safety of pulmonary vein isolation and left atrial complex fractionated atrial electrograms ablation for atrial fibrillation with phased radiofrequency energy and multi-electrode catheters.

AIMS: Recently, a multi-electrode catheter system using phased radiofrequency (RF) energy was developed specifically for atrial fibrillation (AF) ablation: the pulmonary vein ablation catheter (PVAC), the multi-array septal catheter (MASC), and the multi-array ablation catheter (MAAC). Initial results of small trials have been promising: shorter procedure times and low adverse event rates. In a large single-centre registry, we evaluated the adverse events associated with multi-electrode ablation catheter procedures with PVAC alone, or combined with MASC and MAAC. METHODS AND RESULTS: In all, 634 consecutive patients with AF had 663 procedures with multi-electrode ablation catheters, 502 patients with the PVAC alone, 128 patients with PVAC/MASC/MAAC, 29 redo procedures with the PVAC or PVAC/MASC/MAAC, and 4 patients had a complicated transseptal puncture. Major and minor adverse events during 6 month follow-up were registered. In 15 cases (2.3%), major adverse events were seen within the first month after the procedure. These included complicated transseptal puncture (4), stroke (2), transient ischaemic attack (5), acute coronary syndrome (2), femoral pseudoaneurysm (1), and arteriovenous fistulae (1). Minor adverse events were seen in 10.7% at 6 months, mostly due to femoral haematoma (3.9%), and non-significant PV stenosis (5.2%). There was no difference in the occurrence of major adverse events between PVAC alone, or PVAC/MASC/MAAC ablation. CONCLUSION: Ablation with phased RF and multi-electrode catheters is accompanied by a major adverse event rate of 2.3% within 1 month and a minor event rate of 10.7% at 6 months.

Arrhythmia detection after atrial fibrillation ablation: value of incremental monitoring time.

BACKGROUND: After pulmonary vein isolation (PVI), patients need to be followed to analyze the effect of the treatment. We evaluated the influence of the duration of Holter monitoring on the detection of arrhythmia recurrences after a single PVI at 12 months. METHODS: Consecutive patients with paroxysmal atrial fibrillation (AF) underwent successful PVI with phased radiofrequency and pulmonary vein ablation catheter. Follow-up was performed with electrocardiogram at 3, 6, and 12 months and 7-day Holter at 12 months. Symptomatic patients received additional event recording. The 7-day Holters at 12 months were evaluated for documented left atrial tachyarrhythmia recurrences, and each individual day with AF was categorized. RESULTS: At 12 months after the procedure, 21 of the 96 (22%) patients had AF on their 7-day Holter. In the patients with AF recurrence, there was an increase in sensitivity from 53% of a 1-day Holter up to 88% with 4-day Holter, and 100% of a 7-day Holter. Monitoring with duration of less than 4 days resulted in significantly less detection of patients with AF compared to 7-day Holter. CONCLUSIONS: A 4-day Holter at 12 months has an 88% sensitivity for arrhythmia detection, and appears to provide a sufficient monitoring time. Prolonging the monitoring time to 7 days does not significantly increase the yield.

Pulmonary vein anatomy and long-term outcome after multi-electrode pulmonary vein isolation with phased radiofrequency energy for paroxysmal atrial fibrillation.

AIMS: We evaluated the effect of pulmonary vein (PV) anatomical characteristics on PV isolation (PVI) and long-term efficacy of ablation with phased radiofrequency (RF) energy and pulmonary vein ablation catheter (PVAC) multi-electrode catheter. METHODS AND RESULTS: Before the procedure, PV anatomy was visualized by magnetic resonance imaging (MRI). Consecutive patients with paroxysmal atrial fibrillation were treated with the PVAC with successful acute isolation. Follow-up was performed at 3, 6, and 12 months with electrocardiogram and 7-day Holter recording at 6 and/or 12 months. Symptomatic patients received additional event recording. In 110 patients a pre-procedure cardiac MRI was performed. Ninety-seven (88%) had a separate left superior PV and separate left inferior PV, all patients had a separate right superior PV and separate right inferior PV. Fourteen (13%) had a left PV with common trunk and 27 (25%) had a separate right middle PV (RMPV). After a follow-up of 1 year, 57 of 110 (52%) patients were free of AF without anti-arrhythmic drug. No specific anatomical variable that was related to long-term failure could be found. There was a trend for patients with larger veins (>24 mm) or separate RMPV to have a lower efficacy. The number of applications per vein or procedure did not influence long-term outcome. CONCLUSIONS: In patients who have undergone PVI with phased RF energy and PVAC multi-electrode ablation, long-term efficacy is not significantly affected by PV anatomy or number of applications, although a trend for reduced efficacy is seen for PV with diameter >24 mm, and presence of RMPV.

Pulmonary vein isolation and left atrial complex-fractionated atrial electrograms ablation for persistent atrial fibrillation with phased radio frequency energy and multi-electrode catheters: efficacy and safety during 12 months follow-up.

AIMS: Ablation for persistent atrial fibrillation (AF) remains a difficult and time-consuming procedure with varying degrees of success. We evaluated the long-term effects of a novel approach for ablation of persistent AF using multi-electrode catheters. METHODS AND RESULTS: In 89 patients with longstanding persistent AF (>1 year), multi-electrode ablation was performed with a pulmonary vein ablation catheter (PVAC), a multi-array septal catheter (MASC), and a multi-array ablation catheter (MAAC) for ablation of complex-fractionated atrial electrograms (CFAE) at the septum, left atrial (LA) roof, floor, posterior wall, and mitral isthmus. Follow-up was performed at 6 and 12 months with electrocardiogram, 7 days Holter, and occasionally ambulant event recordings. Average procedure and fluoroscopy times were 112 ± 32 and 21 ± 10 min. The pre-specified endpoint of pulmonary vein isolation and LA CFAE ablation was reached in all patients. No procedural complications were observed. At 12 months after a single treatment 44 of 89 (49%) remained in sinus rhythm, including direct current cardioversion in 12 patients. At 12 months, after a redo PVAC/MASC/MAAC, an additional 6 of 15 patients (40%) were free of AF. In 18 of 89 (20%) patients AF was changed to paroxysmal. CONCLUSIONS: In this single centre study, ablation for longstanding persistent AF with the PVAC/MASC/MAAC resulted in 56% freedom of AF at 1 year after 1.2 ± 0.4 procedures. This approach is time efficient and has a favourable safety profile.

Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times.

OBJECTIVE: In implantable cardiac defibrillators (ICDs), long-detection times safely reduce unnecessary and inappropriate therapies. We aimed to evaluate ICD treatment of ventricular arrhythmias in women, compared with men, also taking into account ICD detection. METHODS: The Advance III trial randomised patients implanted with an ICD for primary or secondary prevention in two arms-long and nominal ventricular arrhythmias detection times before therapy delivering (number of intervals needed to detect (NID) 30/40 and 18/24, respectively). The main endpoint of this post hoc analysis was the incidence of ICD therapies evaluated through Kaplan-Meier method and univariate Cox regression models. RESULTS: Overall, 1902 patients (304 women, 65±11 years) were randomised. Women showed a lower risk of ICD therapy (HR 0.63, 95% CI 0.43 to 0.93, p=0.022); this difference was observed only in the long-detection arm (HR 0.37, p=0.013) and not in the short detection arm (HR 0.82, p=0.414). No significant sex differences were observed concerning inappropriate therapies and mortality rate. Long-detection settings significantly reduced overall ICD therapies and appropriate ICD therapies, both in women (overall HR 0.31, p=0.007; appropriate HR 0.33, p=0.033) and in men (overall HR 0.69, p=0.006; appropriate HR 0.73, p=0.048). CONCLUSIONS: In patients with ICDs, the strategy of setting a long-detection time to treat ventricular arrhythmias (NID 30/40) reduces overall delivered therapies, both in women and men, when compared with nominal setting (NID 18/24). The reduction was significantly higher in women. Overall, women were less likely to experience ICD therapies than men; this result was only observed in the long-detection arm. CLINICAL TRIAL REGISTRATION: NCT00617175.

Epicardium-derived cells in development of annulus fibrosis and persistence of accessory pathways.

BACKGROUND: The developmental mechanisms underlying the persistence of myocardial accessory atrioventricular pathways (APs) that bypass the annulus fibrosis are mainly unknown. In the present study, we investigated the role of epicardium-derived cells (EPDCs) in annulus fibrosis formation and the occurrence of APs. METHODS AND RESULTS: EPDC migration was mechanically inhibited by in ovo microsurgery in quail embryos. In ovo ECGs were recorded in wild-type (n=12) and EPDC-inhibited (n=12) hearts at Hamburger-Hamilton (HH) stages 38 to 42. Subsequently, in these EPDC-inhibited hearts (n=12) and in additional wild-type hearts (n=45; HH 38-42), ex ovo extracellular electrograms were recorded. Electrophysiological data were correlated with differentiation markers for cardiomyocytes (MLC2a) and fibroblasts (periostin). In ovo ECGs showed significantly shorter PR intervals in EPDC-inhibited hearts (45+/-10 ms) than in wild-type hearts (55+/-8 ms, 95% CI 50 to 60 ms, P=0.030), whereas the QRS durations were significantly longer in EPDC-inhibited hearts (29+/-14 versus 19+/-2 ms, 95% CI 18 to 21 ms, P=0.011). Furthermore, ex ovo extracellular electrograms (HH 38-42) displayed base-first ventricular activation in 44% (20/45) of wild-type hearts, whereas in all EPDC-inhibited hearts (100%, 12/12), the ventricular base was activated first (P<0.001). Small periostin- and MLC2a-positive APs were found mainly in the posteroseptal region of both wild-type and EPDC-inhibited hearts. Interestingly, in all (n=10) EPDC-inhibited hearts, additional large periostin-negative and MLC2a-positive APs were found in the right and left lateral free wall coursing through marked isolation defects in the annulus fibrosis until the last stages of embryonic development. CONCLUSIONS: EPDCs play an important role in annulus fibrosis formation. EPDC outgrowth inhibition may result in marked defects in the fibrous annulus with persistence of large APs, which results in ventricular preexcitation on ECG. These APs may provide a substrate for postnatally persistent reentrant arrhythmias.

Characterization of in vitro and in vivo lesions made by a novel multichannel ablation generator and a circumlinear decapolar ablation catheter.

INTRODUCTION: The aim of this study is to characterize ablation lesions using varying ratios of bipolar:unipolar energy and to show the feasibility of a circular decapolar pulmonary vein ablation catheter (PVAC) to create transmural lesions in an in vivo porcine superior vena cava (SVC) model. METHODS AND RESULTS: Ablations were performed on (1) isolated blocks of bovine myocardium, (2) thigh muscle preparations (4 pigs), and (3) the junction between SVC and right atrium (6 pigs). Radiofrequency (RF) energy was delivered simultaneously to all electrodes (target temperature 60 degrees C, maximum power 10 W/electrode) with various ratios of bipolar:unipolar energy. (1) In vitro PVAC resulted in circumscript lesions. Changing RF energy mode from unipolar only to bipolar:unipolar 1:1, 2:1 and 4:1 and bipolar only decreased lesion depth significantly (6.7 +/- 0.2 vs. 5.0 +/- 0.2, 4.1 +/- 0.3, 3.6 +/- 0.1 and 3.1 +/- 0.1 mm, P < 0.001). (2) Similar results were obtained in vivo (thigh muscle) showing less deep lesions with more bipolar energy modes (e.g., 5.4 +/- 1.3 for unipolar only vs. 4.1 +/- 0.8 mm for bipolar only, P < 0.05). (3) Ablation at the SVC did not result in device-related complications. All animals survived and were sacrificed after 7 +/- 1 days except for one pig, which died immediately postoperatively from an unknown cause. Macroscopy and microscopy showed circumferential transmural SVC lesions. CONCLUSIONS: Temperature-controlled, power-limited RF energy with the PVAC is feasible for creating circumferential transmural lesions (SVC) that sometimes extended to neighboring structures. Lesion depth can be titrated by varying the bipolar:unipolar energy ratio. This novel ablation system paves the way for single-catheter ablation of AF.

Periostin expression by epicardium-derived cells is involved in the development of the atrioventricular valves and fibrous heart skeleton.

The epicardium is embryologically formed by outgrowth of proepicardial cells over the naked heart tube. Epicardium-derived cells (EPDCs) migrate into the myocardium, contributing to myocardial architecture, valve development, and the coronary vasculature. Defective EPDC formation causes valve malformations, myocardial thinning, and coronary defects. In the atrioventricular (AV) valves and the fibrous heart skeleton isolating atrial from ventricular myocardium, EPDCs colocalize with periostin, a matrix molecule involved in remodeling. We investigated whether proepicardial outgrowth inhibition affected periostin expression and how this related to development of the AV valves and fibrous heart skeleton. Periostin expression by epicardium and EPDCs was confirmed in vitro in primary cultures of human and quail EPDCs. Disturbing EPDC formation in quail embryos reduced periostin expression in the endocardial cushions and AV junction. Disturbed fibrous tissue development resulted in AV myocardial connections reflected by preexcitation electrocardiographic patterns. We conclude that EPDCs are local producers of periostin. Disturbance of EPDC formation results in decreased cardiac periostin levels and hampers the development of fibrous tissue in AV junction and the developing AV valves. The resulting cardiac anomalies might link to Wolff-Parkinson White syndrome with persistent AV myocardial connections.

Persistence of functional atrioventricular accessory pathways in postseptated embryonic avian hearts: implications for morphogenesis and functional maturation of the cardiac conduction system.

BACKGROUND: During heart development, the ventricular activation sequence changes from a base-to-apex to an apex-to-base pattern. We investigated the possibility of impulse propagation through remnants of atrioventricular (AV) connections in quail hearts. METHODS AND RESULTS: In 86 hearts (group A, HH30-34, n=15; group B, HH35-44, n=65; group C, 5 to 6 months, n=6) electrodes were positioned at the left atrium, right ventricular base, left ventricular (LV) base, and LV apex. In group A, LV base activation preceded LV apex activation in the majority of cases (60%; 9 of 15), whereas hearts in group B primarily demonstrated an LV apex-to-base activation pattern (72%; 47 of 65). Interestingly, in group B, the right ventricular base (17%; 11 of 65) or LV base (8%; 5 of 65) exhibited premature activation in 25% (16 of 65) of cases, whereas in 26% (17 of 65), the right ventricular base or LV base was activated simultaneously with the LV apex. Morphological analysis confirmed functional data by showing persistent muscular AV connections in embryonic hearts. Interestingly, all myocardial AV connections stained positive for periostin, a nonmyocardial marker. Longitudinal analysis (HH35-44) demonstrated a decrease in both the number of hearts that exhibited premature base activation (P=0.015) and the number (P=0.004) and width (P=0.179) of accessory AV pathways with developmental stage in a similar time course. In the adult quail hearts, accessory myocardial AV pathways were functionally and morphologically absent. CONCLUSIONS: Thus, impulse propagation through persistent accessory AV connections remains possible at near-hatching stages (HH44) of development, which may provide a substrate for AV reentrant arrhythmias in perinatal life. Periostin positivity and absence of AV pathways in the adult heart suggest that these connections eventually lose their myocardial phenotype, which implicates ongoing AV ring isolation perinatally and postnatally.