Non-invasive three-dimensional electrical activation mapping to predict cardiac resynchronization therapy response: site of latest left ventricular activation relative to pacing site.

AIMS: Pacing remote from the latest electrically activated site (LEAS) in the left ventricle (LV) may diminish response to cardiac resynchronization therapy (CRT). We tested whether proximity of LV pacing site (LVPS) to LEAS, determined by non-invasive three-dimensional electrical activation mapping [electrocardiographic Imaging (ECGI)], increased likelihood of CRT response. METHODS AND RESULTS: Consecutive CRT patients underwent ECGI and chest/heart computed tomography 6-24 months of post-implant. Latest electrically activated site and the distance to LVPS (dp) were assessed. Left ventricular end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modelled non-response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischaemic heart disease (IHD), atrial fibrillation, QRS duration, baseline ejection fraction (EF) and LVESV, comorbidities, use of CRT optimization algorithm, angiotensin-converting enzyme inhibitor(ACE)/angiotensin-receptor blocker (ARB), beta-blocker, diuretics, and dp. Of 111 studied patients [64 ± 11 years, EF 28 ± 6%, implant duration 12 ± 5 months (mean ± SD), 98% had LBBB, 38% IHD], 67% responded at 10 ± 3 months post CRT-implant. Latest electrically activated sites were outside the mid-to-basal lateral segments in 35% of the patients. dp was 42 ± 23 mm [31 ± 14 mm for responders vs. 63 ± 24 mm non-responders (P < 0.001)]. Longer dp and the lack of use of CRT optimization algorithm were the only independent predictors of non-response [area under the curve (AUC) 0.906]. dp of 47 mm delineated responders and non-responders (AUC 0.931). CONCLUSION: The distance between LV pacing site and latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Electrocardiographic imaging to guide ablation of ventricular arrhythmias and agreement between two different systems.

BACKGROUND AND AIM: A recent study using an epicardial-only electrocardiographic imaging (ECGI), suggests that the agreement of ECGI activation mapping and that of the contact mapping for ventricular arrhythmias (VA) is poor. The aim of this study was to assess the diagnostic value of two endo-epicardial ECGI systems using different cardiac sources and the agreement between them. METHODS: We performed 69 ECGI procedures in 52 patients referred for ablation of VA at our center. One system based on the extracellular potentials was used in 26 patients, the other based on the equivalent double layer model in 9, and both in 17 patients. The first uses up to 224 leads and the second just the 12­lead ECG. The localization of the VA was done using a segmental model of the ventricles. A perfect match (PM) was defined as a predicted location within the same anatomic segment, whereas a near match (NM) as a predicted location within the same segment or a contiguous one. RESULTS: 44 patients underwent ablation, corresponding to 58 ECGI procedures (37 with the first and 21 with the second system). The percentage of PMs and NMs was not significantly different between the two systems, respectively 76% and 95%, p = 0.077, and 97% and 100%, p = 1.000. In 14 patients that underwent ablation and had the ECGI performed with both systems, raw agreement for PMs was 79%, p = 0.250 for disagreement. CONCLUSIONS: ECGI systems were useful to identify the origin of the VAs, and the results were reproducible regardless the cardiac source.

Validation of an electrocardiographic marker of low voltage areas in the right ventricular outflow tract in patients with idiopathic ventricular arrhythmias.

BACKGROUND: Previous studies have reported the presence of subtle abnormalities in the right ventricular outflow tract (RVOT) in patients with apparently normal hearts and ventricular arrhythmias (VAs) from the RVOT, including the presence of low voltage areas (LVAs). This LVAs seem to be associated with the presence of ST-segment elevation in V1 or V2 leads at the level of the 2nd intercostal space (ICS). OBJECTIVE: Our aim was to validate an electrocardiographic marker of LVAs in the RVOT in patients with idiopathic outflow tract VAs. METHODS: A total of 120 patients were studied, 84 patients referred for ablation of idiopathic VAs with an inferior axis by the same operator, and a control group of 36 patients without VAs. Structural heart disease including arrhythmogenic right ventricular cardiomyopathy was ruled out in all patients. An electrocardiogram was performed with V1-V2 at the 2nd ICS, and ST-segment elevation ≥1 mm and T-wave inversion beyond V1 were assessed. Bipolar voltage map of the RVOT was performed in sinus rhythm (0.5-1.5 mV color display). Areas with electrograms <1.5 mV were considered LVAs, and their presence was assessed. We compared three groups, VAs from the RVOT (n = 66), VAs from the LVOT (n = 18) and Control group (n = 36). ST-elevation, T-wave inversion and left versus right side of the VAs were tested as predictors of LVAs, respective odds ratio (ORs) (95% confidence interval [CI]) and p values, were calculated with univariate logist regression. Variables with a p < .005 were included in the multivariate analysis. RESULTS: ST-segment elevation, T-wave inversion and LVAs were present in the RVOT group, LVOT group and Control group as follows: (62%, 17%, and 6%, p < .0001), (33%, 29%, and 0%, p = .001) and (62%, 25%, and 14%, p < .0001). The ST-segment elevation, T-wave inversion and right-sided VAs were all predictors of LVAs, respective unadjusted ORs (95% CI), p values were, 32.31 (11.33-92.13), p < .0001, 4.137 (1.615-10.60), p = .003 and 8.200 (3.309-20.32), p < .0001. After adjustment, the only independent predictor of LVAs was the ST-segment elevation, with an adjusted OR (95% CI) of 20.94 (6.787-64.61), p < .0001. CONCLUSION: LVAs were frequently present in patients with idiopathic VAs. ST-segment elevation was the only independent predictor of their presence.

A simplified approach to radiofrequency catheter ablation of idiopathic ventricular outflow tract premature ventricular contractions.

INTRODUCTION: Frequently, low voltage areas (LVAs) and diastolic potentials (DPs) are present at ablation sites in sinus rhythm in patients with idiopathic premature ventricular contractions (PVCs). OBJECTIVE: Validate these findings as substrates for PVCs and evaluate the feasibility of a simplified substrate approach based on LVAs and DPs for ablation of idiopathic outflow tract PVCs, in patients with a low PVC burden during the procedure. METHODS: Prospective single-arm clinical trial at two centers with comparison with a historical group, matched to age and gender. The study group consisted of consecutive patients referred for ablation of frequent idiopathic PVCs with inferior axis, that presented with less than two PVCs/min in first 5 min of the procedure. The ablation was based on fast mapping of the right ventricular outflow tract in sinus rhythm looking for LVAs and DPs, defined as isolated small amplitude potentials occurring after the T wave of the surface echocardiogram. The area with LVAs and DPs was tagged, and a simplified activation mapping of the PVCs was done in that area. The procedure time, success rate, and recurrence rate were compared with the historical group in whom ablation was performed based on activation and pace mapping only. A validation group without PVCs was also studied to assess the prevalence of LVAs and DPs in the general population. RESULTS: The study (n = 38), historical (n = 38), and validation (n = 38) groups did not differ in relation to age or gender. Prevalence of LVAs and DPs was significantly higher in the study group in comparison with the validation group, respectively, 71% versus 11%, p < 0.0001 and 87% versus 8%, p < 0.0001. Procedure time was significantly lower in the study group when comparing to the historical group, 130 (100-164) versus 183 (160-203) min, p < 0.0001 and the success rate was significantly higher, 90% versus 64%, p = 0.013. The recurrence rate in patients with a successful ablation was not significantly different between both groups, Log-rank = 0.125. CONCLUSION: The prevalence of LVAs and DPs was significantly higher in the study group than in the validation group. The proposed approach proved to be feasible, faster, and more efficient than the historical approach.

Assessment of wave front activation duration and speed across the right ventricular outflow tract using electrocardiographic imaging as predictors of the origin of the premature ventricular contractions: A validation study.

AIMS: Evaluate right ventricular outflow tract (RVOT) activation duration (AD) and speed, invasively and with the electrocardiographic imaging (ECGI), as predictors of the origin of the PVCs, validating the ECGI. METHODS: 18 consecutive patients, 8 males, median age 55 (35-63) years that underwent ablation of PVCs with inferior axis and had ECGI performed before ablation. Isochronal activation maps of the RVOT in PVC were obtained with the ECGI and invasively. Total RVOT AD was measured as the time between earliest and latest activated region, and propagation speed by measuring the area of the first 10 ms of activation. Cut-off values for AD, activation speed and number of 10 ms isochrones to predict the origin of the PVCs, were obtained with the ROC curve analysis. Agreement between methods was done with Pearson correlation test and Bland-Altman plot. RESULTS: PVCs originated from the RVOT in 11 (61%) patients. The stronger predictor of PVC origin was the AD. The median AD in PVCs from RVOT was significantly longer than from outside the RVOT, both with ECGI and invasively, respectively 62 (58-73) vs 37 (33-40) ms, p < 0.0001 and 68 (60-75) vs 35 (29-41) ms, p < 0.0001. Agreement between the two methods was good (r = 0.864, p < 0.0001). The cut-off value of 43 ms for AD measured with ECGI predicted the origin of the PVCs with a sensitivity and specificity of 100%. CONCLUSIONS: We found good agreement between ECGI and invasive map. The AD measured with ECGI was the best predictor of the origin of the PVCs.

Frequent premature ventricular contractions. Association of burden and complexity with prognosis according to the presence of structural heart disease.

INTRODUCTION: Premature ventricular contractions (PVC) have been associated with mortality and heart failure (HF) regardless the presence of structural heart disease (SHD). The aim of this study was assessing the impact of burden and complexity of PVCs on prognosis, according to presence of SHD. METHODS: 312 patients were retrospectively evaluated out of 1967 consecutive patients referred for 24-hr Holter at a single hospital, with a PVC count >1% of total beats. Two groups with and without SHD. PVC burden (PVC%), presence of complex forms, incidence of all-cause death, combined outcomes of all-cause death and cardiovascular hospitalizations, HF death and HF hospitalizations and, sudden death (SD) or hospitalizations due to ventricular arrhythmias (VA)were assessed. RESULTS: Premature ventricular contraction burden was 2.7 (IQR: 1.6-6.7). SHD patients had more polymorphic PVCs, 77% versus 65%, p = .022, triplets and episodes of non-sustained ventricular tachycardia (NSVT): 44% versus 27%, p = .002; 30% versus 12%, p < .0001. In idiopathic patients, a PVC% in the third quartile was independently associated with all-cause mortality hazard ratio (HR) 2.288 (1.042-5.026) p = .039, but not in SHD. The complexity of the PVCs was not independently associated with outcomes in both groups. In SHD group, NSVT was associated with lower survival free from SD and VA hospitalizations, p = .028; after multivariable, there was a trend for a higher arrhythmic outcome with NSVT, HR 3.896 (0.903-16.81) p = .068. CONCLUSION: Premature ventricular contractions in SHD showed more complex patterns. In idiopathic patients, a higher PVC count was associated with higher mortality but not is SHD patients. Complexity was not independently associated with worse prognosis.

Right bundle brunch block in patients with acute myocardial infarction is associated with a higher in-hospital arrhythmic risk and mortality, and a worse prognosis after discharge.

INTRODUCTION: Recently, the presence of right bundle brunch block (RBBB) in patients with persistent ischaemic symptoms has been suggested as an indication for emergent coronary angiography. OBJECTIVE: The aim of this study was to assess the prognostic impact of RBBB in patients with acute myocardial infarction (AMI) before the implementation of the recent recommendations. METHODS: We retrospectively studied consecutive patients admitted with AMI between 2011 and 2013. Patients with left bundle brunch block, pacemaker, or nonspecific intraventricular conduction delay were excluded. Patients with RBBB were compared with those without RBBB. Clinical characteristics, in-hospital evolution, and major adverse cardiovascular events (MACE) during follow-up, defined as cardiovascular death, sustained ventricular arrhythmias, acute heart failure syndromes, recurrent myocardial infarction, or acute stroke, were analysed. RESULTS: The analysis included 481 patients. Thirty two patients (6.7%) had RBBB. Patients with RBBB were older. During hospital admission, RBBB patients had a higher rate of sustained ventricular tachycardia and death. Survival curve analysis showed that patients with RBBB had a lower in-hospital survival rate (Log-rank, p = 0.004). After discharge, during a mean follow-up time of 24.3 ± 11.6 months, 53 patients (12%) died. Survival curve analysis showed a lower survival rate free of MACE for those patients with RBBB (Log-rank, p = 0.011). RBBB was independently associated with MACE occurrence (HR 2.17, 95% CI 1.07-4.43; p = 0.033), after adjusting for demographic data, coronary angiography findings, treatment performed, echocardiographic evaluation, and medical therapy. CONCLUSION: Patients with RBBB had a higher rate of in-hospital mortality and arrhythmic events, and an increased risk of MACE during follow-up.

Premature ventricular contractions of the right ventricular outflow tract: is there an incipient underlying disease? New insights from a speckle tracking echocardiography study.

CONTEXT: Premature ventricular contractions (PVCs) originating in the right ventricular outflow tract (RVOT) are traditionally considered idiopathic and benign. Echocardiographic conventional measurements are typically normal. AIMS: To assess whether right ventricle longitudinal strain, determined by two-dimensional speckle tracking echocardiography, differ between RVOT PVCs patients (treated with catheter ablation) and healthy controls. METHODS: We retrospectively selected patients with PVCs from the RVOT who underwent electrophysiological study and catheter ablation between 2016 and 2019. Patients with documented structural heart disease were excluded. Transthoracic echocardiography was performed and right ventricle global longitudinal strain (RV-GLS), free wall longitudinal strain (RVFW-LS) and left ventricle global longitudinal strain (LV-GLS) were determined as well as conventional ultrasound measurements of RV and LV function. RESULTS: We studied 21 patients with RVOT PVCs and 13 controls. Patients with PVCs from the RVOT had lower values of RV-GLS and RVFW-LS compared with the control group (-19.4% versus -22.5%, P = 0.015 and -22.1% versus -25.5, P = 0.041, respectively). They also had lower values of LV-GLS, although still within the normal range (-19.1% versus -20.9%, P = 0.047). Regarding RVOT PVCs patients only, RV-GLS and RVFW-LS had no correlation with the PVCs burden prior to catheter ablation and they did not differ between the patients in whom the catheter ablation was successful and those in whom it was not. RV-GLS also had a positive correlation with RVOT proximal diameter (r = 0.487, P = 0.025). CONCLUSIONS: In this group of RVOT PVCs patients, we found worse RV longitudinal strain values (and therefore sub-clinical myocardial dysfunction) when compared to healthy controls.

Anatomic guided ablation of the atrial right ganglionated plexi is enough for cardiac autonomic modulation in patients with significant bradyarrhythmias.

INTRODUCTION: Cardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe functional bradyarrhythmias, although no consensus exists on the best ablation strategy. The aim of this study was to evaluate if a simplified approach by a purely anatomical guided ablation of just the atrial right GP is enough for the treatment of these patients. METHODS: We prospectively enrolled patients with significant functional bradyarrhythmias and performed endocardial ablation purely guided by 3D electroanatomic mapping directed at the atrial right GP and accessed parameters of parasympathetic modulation and recurrence of bradyarrhythmias. RESULTS: Thirteen patients enrolled (76.9% male, median age 51, 42-63 years). After ablation, a median RR interval shortening of 28.3 (25.6-40.3)% occurred (1111, 937.5-1395.4 ms to 722.9, 652.2-882.4 ms, p = 0.0002). The AH interval also shortened (19, 10.5-35.7%) significantly after the procedure (115, 105-122 ms to 85, 71-105 ms, p = 0.0023) as well as Wenckebach cycle length (11.1, 5.9-17.8% shortening) from 450, 440-510 ms to 430, 400-460 ms, p = 0.0127. On 24-h Holter monitoring there was significant increase in heart rates (HR) of patients after ablation (minimal HR increased from 34 (26-43)bpm to 49 (43-56)bpm, p = 0,0102 and mean HR from 65 (47-72)bpm to 78 (67-87)bpm, p = 0.0004). No patients had recurrence of symptoms or significant bradyarrhythmias during a median follow-up of 8.4 months. CONCLUSIONS: A purely anatomic guided procedure directed only at the atrial right ganglionated plexi seems to be enough as a therapeutic approach for cardioneuroablation in selected patients with significant functional bradyarrhythmias.

Successful ablation of premature ventricular contractions exclusively guided by epicardial and endocardial non-invasive mapping (ECGI) and confirmed by substrate mapping.

Ablation of premature ventricular contractions (PVCs), relies mostly on a detailed activation mapping. This can be impossible to achieve in case of paucity or even absence of PVCs during the procedure. Pacemapping as an alternative has many limitations. We present a case of a patient with very frequent symptomatic PVCs, that on the day of the procedure had total absence of PVCs. We performed successful ablation based exclusively on electrocardiographic imaging confirmed by substrate mapping.

Electrocardiographic imaging (ECGI): What is the minimal number of leads needed to obtain a good spatial resolution?

AIMS: Assess the minimal number of ECGI leads needed to obtain a good spatial resolution. METHODS: We enrolled 20 patients that underwent ablation of premature ventricular or atrial contractions using Carto and ECGI with AMYCARD. We evaluated the agreement regarding the site of origin of the arrhythmia between the ECGI and Carto, the area and diameter of the earliest activation site obtained with the ECGI (EASa and EASd). Based on previous studies with pacemapping, we considered a good spatial resolution of the ECGI when the EASd measured on the isopotential map was less than 18 mm. In presence of agreement the ECGI was reprocessed: a) with half the number of electrode bands (8 leads per electrode band) and b) with 6 electrode bands. RESULTS: The initial map was obtained with 23 (22-23) electrode bands per patient, corresponding to 143 (130-170) leads. Agreement rate was 85%, the median EASa and EASd were: 0.7 (0.5-1.3) cm2 and 9 (8-13) mm. With half the number of electrode bands including 73 (60-79) leads, agreement rate was 80%, the EASa and EASd were: 2.1 (1.5-6.2) cm2 and 16 (14 -28) mm. With only six electrode bands using 38 (30-42) leads, agreement rate was 55%, EASa and EASd were: 4.0 (3.3-5.0) cm2 and 23 (21-25) mm. The number of leads was a predictor of agreement with a good spatial resolution, OR (95% CI) of 1.138 (1.050-1.234), p = .002. According to the ROC curve, the minimal number of leads was 74 (AUC 0.981; 95% CI: 0.949-1.00, p < .0001). CONCLUSION: Reducing the number of leads was associated with a lower agreement rate and a significant reduction of spatial resolution. However, the number of leads needed to achieve a good spatial resolution was less than the maximal available.

A lower left atrial appendage peak emptying velocity in the acute phase of cryptogenic stroke predicts atrial fibrillation occurrence during follow-up.

BACKGROUND: Silent atrial fibrillation is a frequent etiology of cryptogenic stroke. Spontaneous conversion of atrial fibrillation to sinus rhythm results in atrial stunning. OBJECTIVE: To evaluate if the presence of a lower left atrial appendage peak emptying velocity (LAAV) after a cryptogenic stroke is associated with the occurrence of atrial fibrillation (AF). METHODS: We retrospectively selected consecutive patients with an acute ischemic stroke that had a transoesophageal echocardiogram (TEE) performed in the first 30 days of the acute event. Documented AF or potential cardioembolic sources in the TEE were considered exclusion criteria. We assessed the LAAV. During follow-up, we evaluated the occurrence of new-onset AF and the combined endpoint of death or new ischemic stroke. RESULTS: We studied 73 consecutive patients, during a mean follow-up period of 54.9 ± 19.3 months. Seven developed AF, and 13 had the combined endpoint. LAAV was independently associated with AF occurrence (HR: 0.93, 95% CI: 0.88-0.99; P = .016). Patients with a LAAV ≤ 46.5 cm/s (AUC: 0.766, 95% CI: 0.579-0.954; P = .021) had a lower survival rate free from AF occurrence (Log-rank, P < .001) and free from the combined endpoint of death or ischemic stroke (Log-rank, P = .010). CONCLUSION: A lower LAAV was associated with AF occurrence and the combined endpoint of death or ischemic stroke after an initial episode of cryptogenic stroke. Patients with this finding could eventually benefit from long-term cardiac rhythm monitoring.

Non-invasive electrocardiographic imaging in patients with idiopathic premature ventricular contractions from the right ventricular outflow tract: New insights into arrhythmia substrate.

AIMS: The aim of this study was to use non-invasive electrocardiographic imaging (ECGI) to study the electrophysiological properties of right ventricular outflow tract (RVOT) in patients with frequent premature ventricular contractions (PVCs) from the RVOT and in controls. METHODS: ECGI is a combined application of body surface electrocardiograms and computed tomography or magnetic resonance imaging data. Unipolar electrograms are reconstructed on the epicardial and endocardial surfaces. Activation time (AT) was defined as the time of maximal negative slope of the electrogram (EGM) during QRS, recovery time (RT) as the time of maximal positive slope of the EGM during T wave, Activation recovery interval (ARI) was defined as the difference between RT and AT. ARI dispersion (Δ ARI) and RT dispersion (Δ RT) were calculated as the difference between maximal and minimal ARI and RT respectively. We evaluated those parameters in patients with frequent PVCs from the RVOT, defined as >10.000 per 24 h, and in a control group. RESULTS: We studied 7 patients with frequent RVOT PVCs and 17 controls. Patients with PVCs from the RVOT had shorter median RT than controls, in the endocardium and in the epicardium, respectively 380 (239-397) vs 414 (372-448) ms, p = 0.047 and 275 (236-301) vs 330 (263-418) ms, p = 0.047. The dispersion of ARI and of RT in the epicardium was higher than in controls, Δ ARI of 145 (68-216) vs 17 (3-48) ms, p = 0.001 and Δ RT of 201 (160-235) vs 115 (65-177), p = 0.019. CONCLUSION: In this group of patients we found a shorter median RT in the endocardium and in the epicardium of the RVOT and a higher dispersion of the ARI and RT across the epicardium in patients with PVCs from the RVOT when comparing to controls.

Clinical Impact of Oral Anticoagulation in Patients with Atrial High-rate Episodes.

BACKGROUND: Atrial high-rate episodes (AHREs) are common in pacemaker patients. Our aims were to compare patients with AHREs to those without them and to assess if, in those with AHREs, the initiation of oral anticoagulation (OAC) has any clinical impact on the occurrence of ischemic and hemorrhagic events. METHODS: From 2014-2017 we selected patients with pacemaker in whom AHREs were detected. AHREs were defined as episodes lasting more than 6 minutes if the electrogram was available or more than 6 hours if not. We used an age- and gender-matched population with pacemaker but no AHRE as a control group (observational study). Those with AHRE were referred to their assistant physician to decide OAC initiation, based on individual circumstances (interventional study). In interventional study, the primary outcome was a composite of systemic thromboembolism or major bleeding. Secondary outcomes were clinical relevant nonmajor bleeding, major and nonmajor bleeding, CV death, and death from all causes. RESULTS: AHREs were detected in 86 patients: 69 patients initiated OAC and the remaining 17 patients did not. When comparing patients with and without AHRE, baseline characteristics were not different between the groups, except for indexed left atrium volume-40 mL (IQR: 34-50) in AHRE group versus 35 mL (IQR: 34-40) in control group (P = .014). AHREs were associated with future development of atrial fibrillation (AF) and the risk was higher if AHRE duration was superior to 6 hours. Death and cardiovascular (CV) death were not significantly different between the groups with and without AHRE. Primary outcome occurred in 4.9 per 100 person-year in OAC group versus 3.4 per 100 person-year in non-OAC group (HR 1.4, 95% CI .2-11.3, P = .78). Secondary outcomes were not significantly different in the groups. CONCLUSIONS: In this group of patients with pacemakers, the presence of AHREs was useful for predicting the future development of AF and the risk of AF was higher in those with a longer duration of AHRE. In the AHRE group, OAC therapy was not associated with a significant difference in the risk of thromboembolism or major bleeding.

Safety and Long-Term Outcomes of Catheter Ablation of Atrial Fibrillation Using Magnetic Navigation versus Manual Conventional Ablation: A Propensity-Score Analysis.

INTRODUCTION: Whether or not the potential advantages of using a magnetic navigation system (MNS) translate into improved outcomes in patients undergoing atrial fibrillation (AF) ablation is a question that remains unanswered. METHODS AND RESULTS: In this observational registry study, we used propensity-score matching to compare the outcomes of patients with symptomatic drug-refractory AF who underwent catheter ablation using MNS with the outcomes of those who underwent catheter ablation using conventional manual navigation. Among 1,035 eligible patients, 287 patients in each group had similar propensity scores and were included in the analysis. The primary efficacy outcome was the rate of AF relapse after a 3-month blanking period. At a mean follow-up of 2.6 ± 1.5 years, AF ablation with MNS was associated with a similar risk of AF relapse as compared with manual navigation (18.4% per year and 22.3% per year, respectively; hazard ratio 0.81, 95% CI 0.63-1.05; P = 0.108). Major complications occurred in two patients (0.7%) using MNS, and in six patients (2.1%) undergoing manually navigated ablation (P = 0.286). Fluoroscopy times were 21 ± 10 minutes in the manual navigation group, and 12 ± 9 minutes in the MNS group (P < 0.001), whereas total procedure times were 152 ± 52 minutes and 213 ± 58 minutes, respectively (P < 0.001). CONCLUSIONS: In this propensity-score matched comparison, magnetic navigation and conventional manual AF ablations seem to have similar relapse rates and a similar risk of complications. AF ablations with magnetic navigation take longer to perform but expose patients to significantly shorter fluoroscopy times.

Prognostic Value of a Very Prolonged Asystole during Head-Up Tilt Test.

BACKGROUND: Clinical significance and prognosis of a cardioinhibitory response to head-up tilt (HUT) test with a very prolonged asystole (≥30 seconds) is poorly studied. Our aim was to evaluate the treatment (including pacemaker implantation) and prognosis (syncope recurrence, syncope-related trauma, and overall mortality) of patients with a very prolonged asystole on a HUT test. METHODS AND RESULTS: A retrospective study was conducted in two centers between January 2003 and December 2013 and included a total of 2,263 consecutive HUT tests (sensitized with isosorbide dinitrate) performed in 2,247 patients with syncope of unknown etiology. Cardioinhibitory response with asystole was observed in 149 (6.6%) of these tests (44.3% women, mean age 37 ± 18 years old, 16.1% in the nonpharmacological phase), with a median duration of asystole of 10 (6-19) seconds. Very prolonged asystole (≥30 seconds) was documented in 11 (0.5%) patients (45% women; mean age 40 ± 19 years; only one in the nonpharmacological phase, 9 minutes after HUT). The longest pause lasted 63 seconds. In all patients, avoidance of triggering factors and physical counterpressure maneuvers were recommended. Telephone follow-up was performed: in one patient, fludrocortisone was started; tilt training was conducted in one patient and none received a pacemaker. After a median follow-up of 42 (30-76) months, four patients (36%) had syncopal recurrences, one patient had a syncope-related injury (scalp laceration), and no patient died.

Quality indicators in atrial fibrillation ablation (RIQAFA). A national registry from the Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE).

INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is the most common sustained arrhythmia, with significant burden for patients. Catheter ablation is safe and superior for symptom improvement. The purpose of this work was to assess how clinical practice compares with current scientific evidence and quality indicators for AF ablation. METHODS: The Portuguese Association of Arrhythmology, Pacing and Electrophysiology conducted a prospective registry among Portuguese centers to assess clinical practice regarding management of patients referred for ablation and the methodology used in the procedures and related outcomes. RESULTS: A total of 337 patients were referred for ablation, 102 (37.91%) female, age 65 (56-70.8) years. The median CHADS2-VaSC2 thromboembolic risk score was 2 (1-3), and 308 (92.49%) were on anticoagulants. AF was mainly paroxysmal (224, 66.97%) and symptomatic (mEHRA score 3; 2-3). Before ablation most patients (273, 81.49%) underwent cardiac computed tomography and only 24 (7.36%) procedures were performed with uninterrupted anticoagulation. For ablation, Carto® (194; 59.15%) and Ensite® (55; 16.77%) were mainly used, and the preferential strategy was pulmonary vein isolation (316; 94.61%). Acute complications occurred in five (1.49%) patients, while most had symptom improvement at one month (200; 86.21%), sustained at one year. There were 40 (12.6%) relapses within 30 days and 19 (26.39%) at one year. CONCLUSIONS: In a population of patients with AF referred for ablation in Portuguese centers, patient management is provided according to the best scientific evidence and there is a high standard of practice with respect to the quality of AF ablation practice.

Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos.

Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. Here we investigated the dynamics of epithelial-mesenchymal interactions that take place at the earliest stages of thymic and parathyroid organogenesis using the quail-chick model together with a co-culture system capable of reproducing these early events in vitro. The presumptive territories of thymus and parathyroid epithelia were identified in three-dimensionally preserved pharyngeal endoderm of embryonic day 4.5 chick embryos on the basis of the expression of Foxn1 and Gcm2, respectively: the thymic rudiment is located in the dorsal domain of the third and fourth pouches, while the parathyroid rudiment occupies a more medial/anterior pouch domain. Using in vitro quail-chick tissue associations combined with in ovo transplantations, we show that the somatopleural but not the limb bud mesenchyme, can mimic the role of neural crest-derived pharyngeal mesenchyme to sustain development of these glands up to terminal differentiation. Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail-chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. These results show that morphological development and cell differentiation of thymus and parathyroid epithelia require a succession of signals emanating from the associated mesenchyme, among which Bmp4 plays a pivotal role for triggering thymic epithelium specification.

Portrayal of the Notch system in embryonic stem cell-derived embryoid bodies.

We portrayed the Notch system in embryonic stem cell (ESC)-derived embryoid bodies (EBs) differentiating under the standard protocols used to assess yolk sac (YS) hematopoiesis in vitro. Notch receptors and Notch ligands were detected in virtually all cells throughout EB development. Notch 1 and Notch 2, but not Notch 4, were visualized in the nucleus of EB cells, and all these receptors were also observed as patent cytoplasmic foci. Notch ligands (Delta-like 1 and 4, Jagged 1 and 2) were immunodetected mostly as cytoplasmic foci. Widespread Notch 1 activation was evident at days 2-4 of EB differentiation, the time window of hemangioblast generation in this in vitro system. EBs experienced major spatial remodeling beyond culture day 4, the time point coincident with the transition between primitive and multilineage waves of YS hematopoiesis in vitro. At day 6, where definitive YS hematopoiesis is established in EBs, these exhibit an immature densely packed cellular region (DCR) surrounded by a territory of mesodermal-like cells and an outer layer of endodermal cells. Immunolabeling of Notch receptors and ligands was usually higher in the DCR. Our results show that Notch system components are continuously and abundantly expressed in the multicellular environments arising in differentiating EBs. In such an active Notch system, receptors and ligands do not accumulate extensively at the cell surface but instead localize at cytoplasmic foci, an observation that fits current knowledge on endocytic modulation of Notch signaling. Our data thus suggest that Notch may function as a territorial modulator during early development, where it may eventually influence YS hematopoiesis.