Aims: Typical atrial flutter (AFL) is an arrhythmia closely related to atrial fibrillation (AF). In this study, the role of the Holter monitor (HM) in the detection of AF in patients with ablated AFL was analysed.Methods: In 150 patients with successful AFL ablation, a follow-up resulted in repeated face-to-face visits, two echocardiograms (post-ablation and at 1-month), and two 24-hour HM (at 1-month and at 6-month) were performed. The diagnostic efficacy of AF with both HM was compared with analysis of face-to-face monitoring. Atrial arrhythmia burden and their relationship with development of AF were analysed.Results: Forty-one patients were diagnosed with AF (27.3%). In 12 patients, the HM was the only method that detected AF, increasing the diagnostic efficacy in 41%. Atrial premature complexes (APC) [473 (101-473) vs. 20 (39-399); p =0.003] and patients with short atrial arrhythmia runs (AAR) [34 (83%) vs. 46 (42%); p <0.001] were more frequent in the group with AF. The presence of AAR in any HM had a sensitivity of 87.1%, specificity of 57.8%, positive predictive value of 42.5% and negative predictive value of 92.6% to diagnose AF at 1-year. Previous AF, mean APC in 24 hours, and AAR in any HM were predictors of AF in follow-up.Conclusions: HM follow-up after ablation of AFL significantly increases the diagnosis of AF. The burden of atrial arrhythmia and the history of previous AF are independent factors related to the development of AF and they can allow the risk stratification and indicate a more exhaustive monitoring.

The clinical impact of slow ventricular tachycardia (VT), occurring in patients carrying implantable cardiac defibrillators (ICD), is still under debate. From the UMBRELLA registry (multicenter, observational, and prospective study on patients with ICD), 659 episodes of slow VT were observed in 97 patients. Untreated slow VT (n = 93) had longer duration (23.7 min, CI95%: 10–39), compared with episodes treated effectively by anti-tachycardia pacing (ATP; n = 527; 0.32 min, IC95%: 0.22–0, 48) or shock (n = 39; 1 min, CI95%: 0.8–1.2). Despite of longer duration, the time to the first contact with the medical services was similar to those episodes treated by ATP (50 days [CI95%: 45–55] vs. 41 days [CI95%: 39–44]). However, both were significantly longer than the time observed in episodes treated with shock (10 days, CI95%: 6–15). This tendency was maintained with successive interrogations of the device (2nd and 3rd). There were no significant differences in mortality during follow-up (48 ± 16 months), neither other adverse outcomes, between patients who presented untreated slow TV and those who did not (log-rank p = 0.28). In a Cox regression analysis, the variable “presenting untreated episodes of slow VT” was not able to predict mortality. However, being in sinus rhythm (vs. atrial fibrillation, OR: 0.31, p = 0.009), narrower QRS (OR: 1.036, p = 0.037) and diabetes (OR 4.673, p = 0.049) appropriately predict survival. Untreated slow VT does not significantly worsen patient prognosis. Our results support the limitation of therapies to ATP only, thus avoiding therapies that have been associated with increased risk of morbidity and mortality.

(1) Background: The clinical management of Brugada Syndrome (BrS) remains suboptimal. (2) Objective: To explore the role of standard electrocardiogram (ECG) spectral analysis in diagnosis and risk stratification. (3) Methods: We analyzed 337 patients—43 with a spontaneous type I ECG pattern (Spont-BrS), 112 drug induced (Induct-BrS), and 182 with a negative response to the drug challenge (negative responders (NR)). ECGs were processed using the wavelet transform (high frequency: 85 to 130 Hz). (4) Results: The power of the high-frequency content in the ST segment (Total ST Power; nV2Hz−1103) was higher in BrS compared with NR patients (Spont-BrS: 28.126 (7.274–48.978) vs. Induc-BrS: 26.635 (15.846–37.424) vs. NR: 11.13 (8.917–13.343); p = 0.002). No differences were observed between ECG patterns in BrS patients. However, the Total ST Power of the type II or III ECG in NR patients was lower than in the same ECG patterns recorded from BrS patients (BrS: 31.07 (16.856–45.283); vs. NR: 10.8 (7.248–14.352) nV2Hz−1103; p = 0.007). The Total ST Power, age, and family history of BrS were independent predictors of positive responses to drug testing. Comparing models with versus those without Total ST Power, the area under the received operator curve (ROC) curve increased (with 0.607 vs. without 0.528, p = 0.001). Only syncope was associated with an increased risk (follow-up 55.8 ± 39.35 months). However, the area under the ROC curve increased significantly when the Total ST Power was included as a covariate (with 0.784 vs. without 0.715, p = 0.04). (5) Conclusions: The analysis of the high-frequency content of ECG signals increases the predictive capability of clinical variables in BrS patients.

Background: there is increasing interest for computing corrected QT intervals in patients with prolonged depolarization. We aimed to analyze the effect of prolonged QRS in the QT and in the diagnostic accuracy of frequency-correction. Methods and Results: in 28 patients admitted for self-expanding aortic valve implantation, sequential pacing was performed in the AAI mode in two different phases: before and immediately after the release of the prosthesis. We evaluated the accuracy of the Bazett, Fridericia, Framingham and Hodges formulas with the reference of the QT at 60 bpm (QTc/deviation). The widening of the QRS was the main contributor to the QT prolongation (Pearson 0.79; CI95%: 0.75-0.84). Prolongation in other intervals (ST segment and T-wave) significantly contribute in the higher frequency range (p < 0.05). The Bazett's formula displayed the highest QTc/deviation, while Framingham and Hodges retrieved the lowest QTc/deviation and the best fit (p < 0.001). In addition, the Bazett's formula displayed the highest correlation between variations in the QTc/deviation and the widening of the QRS (Pearson coefficient -0.54; p < 0.001) in comparison with the Fridericia, Framingham and Hodges formulas (-0.51, -0.37 and -0.38 respectively; p < 0.001). There was also a linear effect of the heart rate in the QTc/deviation obtained with the Bazett's formula (p = 0.015), not observed for other formulas. Conclusions: The prolonged depolarization of the ventricles introduces direct and linear prolongation in the QT interval, but also a non-linear distortion in cardiac repolarization that contributes for QT prolongation at the higher frequency range. The Bazett's formula displays significantly higher sensitivity to prolongation of ECG intervals.

Brugada syndrome (BrS) is an inherited disease with an increased risk of sudden cardiac death (SCD). However, testing identifies genetic disorders in only 20-30% of patients analysed, indicating a gap in knowledge of its genetic aetiology. Diagnosis relies on ECG, and risk stratification in BrS patients is challenging primarily because of the complexity of the issue. As a result, clinicians fail to provide the appropriate strategy for SCD prevention for many patients. Several variables and interventions are being studied to improve diagnostics and maximise patient protection. In addition, the scientific community must increase efforts to provide patient care according to knowledge and research for improving stratification of risk. In this article, the authors summarise contemporary evidence on clinical variables and provide an overview of future directions in risk stratification and SCD prevention.

Aims:Tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal re-entry (AVNRT) require careful electrophysiologic evaluation for differential diagnosis. We aim to describe the differential behaviour of local ventriculo-atrial (VA) intervals which predicts the tachycardia mechanism.Methods and results:The local VA intervals at the para-Hisian septum were measured under three different situations: (i) tachycardia; (ii) sustained entrainment from the right ventricular apex (RVA); and (iii) continuous pacing from the RVA during sinus rhythm. Differences were computed as follows: Δ-VAentr = VA during entrainment - VA during tachycardia; and Δ-VApac = VA while pacing during sinus rhythm - VA during tachycardia. In contrast to AVNRT, we hypothesized that an invariable retrograde conduction through the septal AP will keep the result of the subtractions close to 0 ms in cases of ortodromic atrioventricular re-entrant tachycardia (AVRT). We analysed 55 atypical AVNRT (45% posterior type) and 82 AVRT (10 anteroseptal, 18 para-Hisian, 12 mid-septal, and 42 posteroseptal). Δ-VAentr was longer for AVNRT (98.5 ± 40.3 ms) compared with septal AP (-5.7 ± 19.3 ms; P < 0.001). A value of 50 ms showed 98.7% sensitivity and 92% specificity (AUC 0.99; 95% CI 0.98-1). According to physiological criteria, a negative Δ-VAentr remains unobserved in the case of AVNRT (positive predictive value 100% for septal AP). Δ-VApac was also longer for AVNRT (66.5 ± 14.6 ms) compared with septal AP (-9.7 ± 3.3 ms; P < 0.001). A value of 50 ms showed 100% sensitivity and 74% specificity (AUC 0.86; 95% CI 0.76-0.93).Conclusions:Delta of the local VA intervals enables distinction between atypical AVNRT and AVRT mediated by septal AP.

Background and objectivesEarly failure of Biotronik Linox and Linox Smart leads (Biotronik, Berlin, Germany) has been reported in numerous recent publications. The aim of this study was to assess the performance of this lead compared with that of two other contemporary leads. MethodsWe conducted an ambispective study of all consecutive first implantations of defibrillator leads carried out in our center: Endotak (model 148, 158, Boston Scientific, Marlborough, MA, USA) (n=173), Sprint Quattro (model 6644, 6947, Medtronic, Dublin, Ireland) (n=145), and Linox Smart (Biotronik, model SD 65/16) (n=120). ResultsDuring a median follow-up of 4.6 2.1 years, failure occurred in nine Linox Smart (7.5%), one Endotak Reliance (0.6%), and no Sprint Quattro leads. The survival probability of the Linox Smart group was significantly lower than that of the Endotak and Sprint Quattro groups measured by the log-rank test (Linox vs Endotak; P<0.001 and Linox vs Sprint Quattro; P<0.001). Nonphysiological signals not due to external interference were observed in all Linox Smart leads, with normal parameters and without visible anomalies on chest x-ray. ConclusionsIn this single-center experience, the survival rate of Linox Smart leads was 88% at 5 years of follow-up, which was significantly lower than that of the other leads. Comprehensive vigilance of Linox Smart leads, including home monitoring, may be advisable to facilitate early detection of lead failure and avoid inappropriate shocks.

Aims Sensitivity to flecainide testing results in suboptimal findings in patients with Brugada syndrome (BrS), leading to safety concerns. Because cardiac syncope effectively predicts outcomes in BrS, we aimed to explore its predictive value in a large cohort of negative and positive responders (NR and PR) to standard flecainide testing. Methods and results We analysed the data of 251 consecutive patients, 177 NR vs. 74 PR, to flecainide testing, performed according to standard recommendations. Cardiac syncope was defined as syncope presenting without prodromal symptoms and in the absence of any specific situation. Comparing PR with NR, there were no differences regarding age (39 ± 15 vs. 44 ± 13 years; P = 0.052), male gender (70.1% vs. 66.2%; P = 0.553), and family history of sudden cardiac death in relatives younger than 45 years (27% vs. 27%; P = 1). Cardiac syncope was more frequent in PR (12.2% vs. 4%; P = 0.022), and previous sudden cardiac arrest (SCA) was documented only in PR (5.4% vs. 0%; P = 0.007). During the follow-up period (6.2 ± 3.3 years), one NR, who had previously experienced cardiac syncope, developed SCA 3 months after flecainide testing. Following resuscitation, a type I electrocardiogram was spontaneously recorded. The follow-up event rate was higher in patients with cardiac syncope, both in PR and in NR (P < 0.001 both). In a multivariate analysis, cardiac syncope was the unique variable that predicted adverse outcomes (hazard ratio 14.9, 95% confidence interval 1.84-121.25; P = 0.011). Conclusions In patients with false-negative responses to the provocative testing with flecainide, cardiac syncope predicts SCA, allowing a more extensive and individualized evaluation.

Background: In human long-standing persistent atrial fibrillation, rotors potentially explain atrial fibrillation maintenance, but their ablation remains controversial. We aimed to explore original phase/frequency mapping methods to locate rotors and track changes induced by their ablation. Methods and Results: Thirteen patients with long-standing persistent atrial fibrillation (duration, 12–72 months) underwent phase/frequency mapping (Hilbert/Fourier transforms; CARTO-Finder) of the left and right atria (PentaRay catheter). A rotor domain was defined as an area displaying at least 3 consecutive rotations. Ablation was performed by circumferential pulmonary vein isolation plus linear ablation of extrapulmonary rotor domains. We identified 19 rotor domains in 10 patients (1.8±1.1 per patient; 7 in the right atrium versus 12 in the left atrium; 15 extrapulmonary). Overall, rotor domains (9.2±2.2 rotations) displayed higher frequency of activation (6.41 Hz; 95% confidence interval, 6.24–6.57) than nonrotor domains (6.17 Hz; 95% confidence interval, 6.1–6.23; P =0.021), with interatrial frequency gradients established by the spatial location of the rotor domain ( P =0.016). Fibrillatory conduction was suggested as a decrease in the frequency of the slower atria after ablation close to main interatrial conduction fascicles ( P =0.035). Ablation of rotor domains (ablation line, 3.5±0.9 cm) effectively decreased the frequency of activation in both ipsilateral and contralateral atria ( P <0.05 for both), whereas ablation of nonrotor domains did not. Acute conversion to sinus rhythm was observed in 2 patients after ablation of rotor domains. At 1-year follow-up, 70% remained in sinus rhythm (85% out-of-antiarrhythmic drugs). Conclusions: Rotor domains appropriately explain long-standing persistent atrial fibrillation physiology at its frequency content. Their ablation effectively modifies dynamics on restricted ablation.

Our aim was to characterize a stepwise approach in cavotricuspid isthmus ablation for typical atrial flutter in a prospective, noncrossover randomized study.

Background In human long-standing persistent atrial fibrillation, rotors potentially explain atrial fibrillation maintenance, but their ablation remains controversial. We aimed to explore original phase/frequency mapping methods to locate rotors and track changes induced by their ablation. Methods and Results Thirteen patients with long-standing persistent atrial fibrillation (duration, 12–72 months) underwent phase/frequency mapping (Hilbert/Fourier transforms; CARTO-Finder) of the left and right atria (PentaRay catheter). A rotor domain was defined as an area displaying at least 3 consecutive rotations. Ablation was performed by circumferential pulmonary vein isolation plus linear ablation of extrapulmonary rotor domains. We identified 19 rotor domains in 10 patients (1.8±1.1 per patient; 7 in the right atrium versus 12 in the left atrium; 15 extrapulmonary). Overall, rotor domains (9.2±2.2 rotations) displayed higher frequency of activation (6.41 Hz; 95% confidence interval, 6.24–6.57) than nonrotor domains (6.17 Hz; 95% confidence interval, 6.1–6.23; P=0.021), with interatrial frequency gradients established by the spatial location of the rotor domain (P=0.016). Fibrillatory conduction was suggested as a decrease in the frequency of the slower atria after ablation close to main interatrial conduction fascicles (P=0.035). Ablation of rotor domains (ablation line, 3.5±0.9 cm) effectively decreased the frequency of activation in both ipsilateral and contralateral atria (P<0.05 for both), whereas ablation of nonrotor domains did not. Acute conversion to sinus rhythm was observed in 2 patients after ablation of rotor domains. At 1-year follow-up, 70% remained in sinus rhythm (85% out-of-antiarrhythmic drugs). Conclusions Rotor domains appropriately explain long-standing persistent atrial fibrillation physiology at its frequency content. Their ablation effectively modifies dynamics on restricted ablation.

Background Debate regarding the prognosis of asymptomatic patients with Brugada syndrome (BrS) is possibly affected by the selection bias of survivors of sudden cardiac arrest (SCA). We aimed to determine variables influencing surveillance after SCA. Methods We analyzed a BrS cohort of 145 patients belonging to 37 families. We compared the clinical data and circumstances surrounding SCA (i.e., place of occurrence and people accompanying the subject) in 10 patients who survived an episode of SCA (Group A) vs. 27 deceased relatives (first or second degree) who suffered sudden cardiac death (SCD; Group B). Information concerning Group B was agreed upon by at least 3 relatives. A sub-analysis was performed considering families carrying a mutation in SCN5A (Group B-Mutant). Results Syncope was unique in predicting SCA in the BrS cohort. Comparing Groups A vs. B, there were no differences in the mean age at time of SCA/SCD (46.2 [SD 17.1] vs. 39.9 [SD 14.5] years; p = 0.271), gender (male 60% vs. 74.1%; p = 0.442), prior cardiomyopathy (0%), administration of cardiovascular treatments (anti-hypertensive and lipid-lowering drugs; 20% vs. 14.8%; p = 0.653) or conventional cardiovascular risk factors. Environmental circumstances surrounding the SCA/SCD were not significantly different between groups. Prior syncope was more frequent in Group A (80% vs. 3.7%; p < 0.001) and unique in predicting surveillance (p < 0.001). Group B-Mutant displayed equivalent data. Conclusions A previous syncope, as an alarm symptom, might contribute to better surveillance of SCA compared with subjects with SCA as the debut of BrS. The latter might behave as a factor of selection bias.

A large number of studies have investigated neural correlates of consciousness in adults. However, knowledge about brain function in children with disorders of consciousness (DOC) is very limited. We suggest that EEG recordings during sleep are a promising approach. In healthy adults as well as in children, it has been shown that the activity of sleep slow waves (EEG spectral power 1–4.5 Hz), the primary characteristic of deep sleep, is dependent on use during previous wakefulness. Thus the regulation of slow wave activity (SWA) provides indirect insights into brain function during wakefulness.In the present study, we investigated high-density EEG recordings during sleep in ten healthy children and in ten children with acquired brain injury, including five children with DOC and five children with acquired brain injury without DOC. We used the build-up of SWA to quantify SWA regulation.Children with DOC showed a global reduction in the SWA build-up when compared to both, healthy children and children with acquired brain injury without DOC. This reduction was most pronounced over parietal brain areas. Comparisons within the group of children with DOC revealed that the parietal SWA build-up was the lowest in patients showing poor outcome. Longitudinal measurements during the recovery period showed an increase in parietal SWA build-up from the first to the second sleep recording.Our results suggest that the reduced parietal SWA regulation may represent a characteristic topographical marker for brain network dysfunction in children with DOC. In the future, the regulation of SWA might be used as a complementary assessment in adult and paediatric patients with DOC.

Background— Differential diagnosis between tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal reentry can be challenging. We hypothesized that an immediate versus delayed pace-related advancement of the atrial electrogram, once the local septal parahisian ventricular electrogram (SVE) has been advanced, may help in this diagnosis. Methods and Results— We focused on differential timing between SVE and atrial signals at the initiation of continuous right ventricular apical pacing during tachycardia. SVE advancement preceding atrial reset was defined as SVE advanced by the paced wave fronts while atrial signal continued at the tachycardia cycle. We analyzed 51 atypical atrioventricular nodal reentry (45% posterior type) and 80 AP tachycardias (anteroseptal [10], parahisian [18], midseptal [12], and posteroseptal [40]). SVE advancement preceding atrial reset was observed in 98% of atrioventricular nodal reentries during 4±1.1 cycles; this phenomena was observed in 6 (8%) of the atrioventricular reentrant tachycardia mediated by septal AP ( P <0.001; sensitivity 98%; specificity 93%; positive predictive value 90%; negative predictive value 99%) and lasted 1 single cycle ( P <0.001). Right posteroseptal AP tachycardias were distinctly characterized by atrial reset preceding SVE advancement (with ventricular fusion; specificity 100%; positive predictive value 100%). In 11 cases, it was impossible to achieve sustain entrainment. In all of them, the differential responses at the entrainment attempt allowed for appropriate diagnosis. Conclusions— The differential response of the SVE and the atrial electrogram at the initiation of continuous right ventricular apical pacing during tachycardia effectively distinguishes between atypical atrioventricular nodal reentry and atrioventricular reentrant tachycardia mediated by septal APs.

The mechanisms of atrial fibrillation (AF) are incompletely understood. In the time domain, intracardiac recordings of AF reveal atrial electrical activity that seems disorganized and unpredictable. However, in the frequency domain, well-defined spatially distributed gradients of local excitation frequency, demonstrated in both animal experiments and humans, strongly support the idea that AF is organized and driven by a limited number of high-frequency sources (rotors). 1 Mansour M. Mandapati R. Berenfeld O. Chen J. Samie F.H. Jalife J. Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart. Circulation. 2001; 103: 2631-2636 Crossref PubMed Scopus (318) Google Scholar , 2 Atienza F. Almendral J. Moreno J. et al. Activation of inward rectifier potassium channels accelerates atrial fibrillation in humans: evidence for a reentrant mechanism. Circulation. 2006; 114: 2434-2442 Crossref PubMed Scopus (221) Google Scholar The best known approach to quantifying such gradients relies on the use of fast Fourier transformation (FFT) to disperse the power spectral components of a local electrogram. The dominant frequency (DF) component is the frequency with the highest peak in the power spectrum. 3 Berenfeld O. Ennis S. Hwang E. Hooven B. Grzeda K. Mironov S. Yamazaki M. Kalifa J. Jalife J. Time- and frequency-domain analyses of atrial fibrillation activation rate: the optical mapping reference. Heart Rhythm. 2011; 8: 1758-1765 Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Simultaneous or sequential FFT analysis of multiple electrograms reveals the spatial distribution of DFs and provides clear demonstration that AF is highly organized. 4 Mandapati R. Skanes A. Chen J. Berenfeld O. Jalife J. Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation. 2000; 101: 194-199 Crossref PubMed Scopus (607) Google Scholar

BACKGROUND Time-dependent variability of electrocardiogram (ECG) in patients with Brugada syndrome could affect the interpretation of provocative testing.OBJECTIVE The aim of this study was to characterize ECG changes during and after flecainide infusion.METHODS We studied 59 consecutive patients. The ECG was continuously analyzed during the first 30 minutes of provocative testing, and a single ECG was recorded 60 minutes later. We analyzed CYP2D6 and CYP3A5 variants affecting flecainide metabolism and performed blinded measurements at lead II.RESULTS At baseline, ECG patterns were classified as follows: type II in 31 patients (53%), type III in 15 (25%), and normal ECG in 13 (22%). Because of induction of type I ECG, the percentage of responders progressively increased with longer recording time periods (6.8% in 10 minutes vs 11.9% in 20-30 minutes vs 18.6% in 90 minutes; P < .01). Four patients displayed a late response, which was evidenced 90 minutes after the initiation of provocative testing. ORS width differentially increased between responders and nonresponders (P < .01), with a maximum QRS width of 110 ms during the first 30 minutes being effective for identifying possible late responders (sensitivity 100%; specificity 85.6%; positive predictive value 88%; negative predictive value 100%). The incidence of CYP2D6 variants was lower in late responders than in early or delayed responders (0% vs 75% vs 100%; P = .04), while a homogeneous distribution of CYP3A5*3/*3 was observed in our population.CONCLUSION Response to flecainide exhibits time-dependent variability of ECG patterns and intervals. Longer periods of ECG recording increase the recognition probability of type I ECG.