Anatomical and Electrophysiological Characteristics of Dual-Loop Re-Entry in Atypical Atrial Flutter: Implications for Mapping and Catheter Ablation.

Background: Atypical atrial flutter (AFL) can be challenging to ablate, especially when involving dual-loop re-entry. We sought to assess the electroanatomical characteristics of single- and dual-loop AFLs in patients undergoing catheter ablation. Methods: We analyzed 25 non-cavotricuspid isthmus-dependent macro-re-entrant AFL in 19 consecutive patients. Three-dimensional high-density activation mapping was performed, and active re-entry loops were confirmed by entrainment mapping. Results: Of 25 AFLs (24 left, 1 right atrial), 13 (52%) exhibited dual-loop re-entry. The most common circuits included, in 6/13 (46% of dual loops), a perimitral re-entry with a second loop around the right/left pulmonary veins (PV) and, in 6/13 (46%), involved a right PV ostium with a second loop around either a functional conduction block or another PV. Ablation at the common isthmus of dual-loop AFLs and at the critical isthmus of single-loop AFLs terminated the arrhythmia more frequently than ablation at a secondary isthmus of dual-loop AFLs (5/6 (83%) and 8/11 (73%) versus 1/8 (13%), respectively, p = 0.013). Conclusions: More than half of AFLs exhibited a dual-loop re-entrant mechanism. Most critical isthmuses were found at the mitral isthmus, the left atrial roof or right PV ostia. Ablation targeting the common isthmus resulted in a higher termination rate.

ATE Score Diagnostic Accuracy for Predicting the Absence of Intra-Atrial Thrombi Before AF Ablation.

BACKGROUND: In a preliminary study in patients hospitalized for catheter ablation of atrial fibrillation (AF), the atrial thrombus exclusion (ATE) score (stroke, hypertension, heart failure, and D-dimers >270 ng/mL) was developed to rule out the diagnosis of intra-atrial thrombus, with a negative predictive value (NPV) of 100%, and to avoid performing transesophageal echocardiography (TEE). OBJECTIVES: The present study was designed to prospectively confirm the NPV of the ATE score in an independent population. METHODS: Consecutive patients hospitalized for catheter ablation of AF or left atrial tachycardia (LAT) were prospectively enrolled in a multicenter study. D-dimer levels were measured within 48 hours before ablation. An ATE score of 0 was considered predictive of no thrombus. TEE was routinely performed at the beginning or just before the ablation procedure. The primary endpoint was the presence of atrial thrombus diagnosed by TEE. RESULTS: The analysis included 3,072 patients (53.3% paroxysmal AF, 36.7% persistent AF, and 10% LAT). A thrombus was detected in 29 patients (0.94%; 95% CI: 0.63%-1.35%), all on appropriate anticoagulant therapy. An ATE score of 0 was observed in 818 patients (26.6%), and the sensitivity, specificity, positive predictive value, and NPV were 93.1%, 26.8%, 1.2%, and 99.8%, respectively. Follow-up of the 2 false negative patients revealed the persistence of chronic organized thrombi. CONCLUSIONS: In patients hospitalized for catheter ablation of AF or LAT, the ATE score identifies a population at very low risk for atrial thrombus. In consultation with the patient, the cardiologist may consider not performing a preoperative TEE in case of an ATE score of 0.

Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial.

AIMS: Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. METHODS AND RESULTS: We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. CONCLUSION: Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TRIAL REGISTRATION: TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

ECMELLA as a bridge to heart transplantation in refractory ventricular fibrillation: A case report.

Background: Extracorporeal membrane oxygenation (ECMO) is an effective cardiorespiratory support technique in refractory cardiac arrest (CA). In patients under veno-arterial ECMO, the use of an Impella device, a microaxial pump inserted percutaneously, is a valuable strategy through a left ventricular unloading approach. ECMELLA, a combination of ECMO with Impella, seems to be a promising method to support end-organ perfusion while unloading the left ventricle. Case summary: The present case report describes the clinical course of a patient with ischemic and dilated cardiomyopathy who presented with refractory ventricular fibrillation (VF) leading to CA in the late postmyocardial infarction (MI) period, and who was successfully treated with ECMO and IMPELLA as a bridge to heart transplantation. Discussion: In the case of CA on VF refractory to conventional resuscitation maneuvers, early extracorporeal cardiopulmonary resuscitation (ECPR) associated with an Impella seems to be the best strategy. It provides organ perfusion, left ventricular unloading, and ability for neurological evaluation and VF catheter ablation before allowing heart transplantation. It is the treatment of choice in cases of end-stage ischaemic cardiomyopathy and recurrent malignant arrhythmias.

Early and Late Postoperative Tachyarrhythmias in Children and Young Adults Undergoing Congenital Heart Disease Surgery.

The population of patients with congenital heart disease is constantly growing with an increasing number of individuals reaching adulthood. A significant proportion of these children and young adults will suffer from tachyarrhythmias due to the abnormal anatomy, the hemodynamic burden, or as a sequela of surgical treatment. Depending on the underlying mechanism, arrhythmias may arise in the early postoperative period (hours to days after surgery) or in the late postoperative period (usually years after surgery). A good understanding of the electrophysiological characteristics and pathophysiological mechanisms is therefore crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, risk factors, pathophysiological insights, electrophysiological features, and therapy regarding tachyarrhythmias in children and young adults undergoing reparative surgery for congenital heart disease. The evolution and latest data on treatment options, including pharmacological therapy, ablation procedures, device therapy decision, and thromboprophylaxis, are summarized. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

Safety, Efficacy and Prognostic Benefit of Atrial Fibrillation Ablation in Heart Failure with Preserved Ejection Fraction.

Up to 65% of patients with heart failure with preserved ejection fraction (HFpEF) develop AF during the course of the disease. This occurrence is associated with adverse outcomes, including pump failure death. Because AF and HFpEF are mutually reinforcing risk factors, sinus rhythm restoration may represent a disease-modifying intervention. While catheter ablation exhibits acceptable safety and efficacy profiles, no randomised trials have compared AF ablation with medical management in HFpEF. However, catheter ablation has been reported to result in lower natriuretic peptides, lower filling pressures, greater peak cardiac output and improved functional capacity in HFpEF. There is growing evidence that catheter ablation may reduce HFpEF severity, hospitalisation and mortality compared to medical management. Based on indirect evidence, early catheter ablation and minimally extensive atrial injury should be favoured. Hence, individualised ablation strategies stratified by stepwise substrate inducibility provide a logical basis for catheter-based rhythm control in this heterogenous population. Randomised trials are needed for definitive evidence-based guidelines.

[Electrocardiographic abnormalities in the setting of acute central nervous system pathology]. / Anomalies de l'ECG secondaires à une lésion du système nerveux central.

Up to 90% of patients with acute central nervous system lesions, such as stroke, exhibit secondary ECG abnormalities, including ST elevation/depression, T wave inversion, prominent U wave, prolonged QTc interval, sinus bradycardia/pause and atrioventricular block. The pathophysiology involves autonomic nervous system disturbance resulting in altered ventricular repolarization gradients, or even myocardial lesions. Clinical assessment aims at distinguishing asymptomatic neurogenic ECG abnormalities from organic heart conditions such as Takotsubo syndrome, myocardial infarction and chronic coronary syndromes. Serial ECG, cardiac biomarkers and echocardiography should be performed, followed by targeted work-up in selected patients. Prolonged QT, arrhythmias or hemodynamic compromise require continuous monitoring and standard management.

Jusqu'à 90 % des patients souffrant de lésions neurologiques aiguës telles que l'AVC présentent des anomalies ECG neurogènes incluant : sus ou sous-décalage ST, onde T inversée, onde U proéminente, prolongement du QTc, bradycardie/pause sinusale et bloc atrioventriculaire. Leur cause semble être une dérégulation neurovégétative provoquant des gradients de repolarisation ventriculaire, voire des lésions myocardiques. Le bilan doit différencier les nombreux patients avec ECG neurogène asymptomatique de ceux présentant une cardiopathie telle qu'un syndrome de Takotsubo, un infarctus ou une maladie coronarienne stable. Le bilan inclut ECG sérié, biomarqueurs cardiaques et échocardiographie, suivis d'un bilan ciblé chez des patients sélectionnés. Un QT long, des arythmies ou une instabilité hémodynamique imposent un monitoring et les mesures habituelles.

The dimerization mechanism of the N-terminal domain of spider silk proteins is conserved despite extensive sequence divergence.

The N-terminal (NT) domain of spider silk proteins (spidroins) is crucial for their storage at high concentrations and also regulates silk assembly. NTs from the major ampullate spidroin (MaSp) and the minor ampullate spidroin are monomeric at neutral pH and confer solubility to spidroins, whereas at lower pH, they dimerize to interconnect spidroins in a fiber. This dimerization is known to result from modulation of electrostatic interactions by protonation of well-conserved glutamates, although it is undetermined if this mechanism applies to other spidroin types as well. Here, we determine the solution and crystal structures of the flagelliform spidroin NT, which shares only 35% identity with MaSp NT, and investigate the mechanisms of its dimerization. We show that flagelliform spidroin NT is structurally similar to MaSp NT and that the electrostatic intermolecular interaction between Asp 40 and Lys 65 residues is conserved. However, the protonation events involve a different set of residues than in MaSp, indicating that an overall mechanism of pH-dependent dimerization is conserved but can be mediated by different pathways in different silk types.

Changes in LA volume and diameter correlate with mechanisms of recurrence after paroxysmal AF ablation.

Papathanasiou et al point out that the two different methods of LA volume and diameter measurement in our recent publication could limit the significance of the correlations we reported with PV reconnection and non-PV foci as mechanisms of post AF ablation recurrence. While we acknowledge the lack of statistically significant correlations of smaller echo derived LA diameter with PV reconnection or of a larger angiographic LA volume with non-PV foci, the congruent confidence intervals of this correlation suggest a statistical trend. Non-uniform LA dimensional changes as an expression of structural remodelling may also be a possible explanation. Published data indicates that angiographic LA volumes consistently exhibit a positive bias compared to echocardiographic volumes but do provide intra-procedural measurements better correlating with gold standard techniques like CT or MRI. Finally we agree with Papathanasiou et al that dynamic changes in LA dimensions likely correlate with early and late mechanisms of recurrence and merit prospective studies.

The significance of pulmonary veins isolation radiofrequency time and the evolution of left atrium volume on a twelve-year observational follow-up of paroxysmal atrial fibrillation patients.

AIMS: Pulmonary vein isolation (PVI) is the treatment of choice of paroxysmal atrial fibrillation (PAF). However, radiofrequency delivery at extra-PV sites may be additionally required. We compared clinical and procedural characteristics of patients undergoing PVI alone versus adjunctive extra-PV substrate modification, at first procedure and repeat procedures for AF recurrence. METHODS: 587 patients with PAF undergoing radiofrequency (RF) ablation were retrospectively included. Extra-PV ablation was performed in case of sustained AF despite PVI, or at re-do procedures without PV conduction recovery. Demographic, clinical and electrophysiological predictors of survival without re-intervention were analysed in patients' groups having undergone one (G1), two (G2) or three or more procedures (G3). RESULTS: At baseline procedure, PV RF ablation time was shorter in G1 compared to G2/G3 whereas extra-PV RF ablation time was greater in G3 compared to G1. The proportion of patients requiring PV re-isolation decreased with repeat procedures. Smaller LA before procedure 1 (p1) or p2 was associated with PV reconnection at p2. Conversely larger LA before p1 was associated with extra-PV substrate modification at p2. Late re-do procedure timing (>1yr) was associated with increasing LA volume. Only longer PV and total RF time predicted poorer survival free from AF without re-intervention. CONCLUSION: Longer PV RF time predicted requirement for re-ablation during follow-up. Smaller LA size predicted an increased probability of PV reconnection and decreased extra-PV substrate modification at p2. LA size decreased in patients undergoing early re-intervention, whereas it increased in patients undergoing re-intervention later on suggesting ongoing remodelling or progression.

Silent brain infarcts impact on cognitive function in atrial fibrillation.

AIMS: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. METHODS AND RESULTS: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. CONCLUSION: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844.

Long-term risk of adverse outcomes according to atrial fibrillation type.

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.

Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European heart rhythm association and European society of cardiology working group on ecardiology in collaboration with the heart rhythm society, Asia pacific heart rhythm society, Latin American Heart rhythm society and computing in cardiology

Abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (I) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (I) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e. g. catheter­electrode combinations) for signal processing (e. g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

Impact of SMART Pass filter in patients with ajmaline-induced Brugada syndrome and subcutaneous implantable cardioverter-defibrillator eligibility failure: results from a prospective multicentre study.

AIMS: Ajmaline challenge can unmask subcutaneous implantable cardioverter-defibrillator (S-ICD) screening failure in patients with Brugada syndrome (BrS) and non-diagnostic baseline electrocardiogram (ECG). The efficacy of the SMART Pass (SP) filter, a high-pass filter designed to reduce cardiac oversensing (while maintaining an appropriate sensing margin), has not yet been assessed in patients with BrS. The aim of this prospective multicentre study was to investigate the effect of the SP filter on dynamic Brugada ECG changes evoked by ajmaline and to assess its value in reducing S-ICD screening failure in patients with drug-induced Brugada ECGs. METHODS AND RESULTS: The S-ICD screening with conventional automated screening tool (AST) was performed during ajmaline challenge in subjects with suspected BrS. The S-ICD recordings were obtained before, during and after ajmaline administration and evaluated by the means of a simulation model that emulates the AST behaviour with and without SP filter. A patient was considered suitable for S-ICD if at least one sensing vector was acceptable in all tested postures. A sensing vector was considered acceptable in the presence of QRS amplitude >0.5 mV, QRS/T-wave ratio >3.5, and sense vector score >100. Of the 126 subjects (mean age: 42 ± 14 years, males: 61%, sensing vectors: 6786), 46 (36%) presented with an ajmaline-induced Brugada type 1 ECG. Up to 30% of subjects and 40% of vectors failed the screening during the appearance of Brugada type 1 ECG evoked by ajmaline. The S-ICD screening failure rate was not significantly reduced in patients with Brugada ECGs when SP filter was enabled (30% vs. 24%). Similarly, there was only a trend in reduction of vector-failure rate attributable to the SP filter (from 40% to 36%). The most frequent reason for screening failure was low QRS amplitude or low QRS/T-wave ratio. None of these patients was implanted with an S-ICD. CONCLUSION: Patients who pass the sensing screening during ajmaline can be considered good candidates for S-ICD implantation, while those who fail might be susceptible to sensing issues. Although there was a trend towards reduction of vector sensing failure rate when SP filter was enabled, the reduction in S-ICD screening failure in patients with Brugada ECGs did not reach statistical significance. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique Identifier NCT04504591.

Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology.

We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.