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IntroductionThe precise pathophysiology of common atrial flutter remains imperfectly known. The mechanisms of arrhythmia initiation and the role of areas of slow conducting myocardium and functional block are still debated topics.MethodsWe conducted a detailed electrophysiological study of a patient to illustrate and refine these concepts. Prior to CTI ablation, electrophysiological study and electro-anatomical mapping were performed, focusing on initiation and maintenance mechanisms of the arrhythmia.ResultsThe initiation of common atrial flutter takes place on the septal aspect of the cavo-tricuspid isthmus where functional unidirectional conduction block occurs. The direction of activation is therefore frequently counter-clockwise, and the arrhythmia stabilizes around the vena cavas and sinus venosus/crista terminalis region. No conduction slowing is present.ConclusionsCommon atrial flutter initiates when functional unidirectional conduction block occurs on the septal cavotricuspid isthmus. Its rotation is limited by anatomical and functional boundaries.

Focal sources (FS) are believed to be important triggers and a perpetuation mechanism for paroxysmal atrial fibrillation (AF). Detecting FS and determining AF sustainability in atrial tissue can help guide ablation targeting. We hypothesized that sustained rotors during FS-driven episodes indicate an arrhythmogenic substrate for sustained AF, and that non-invasive electrical recordings, like electrocardiograms (ECGs) or body surface potential maps (BSPMs), could be used to detect FS and AF sustainability. Computer simulations were performed on five bi-atrial geometries. FS were induced by pacing at cycle lengths of 120-270 ms from 32 atrial sites and four pulmonary veins. Self-sustained reentrant activities were also initiated around the same 32 atrial sites with inexcitable cores of radii of 0, 0.5 and 1 cm. FS fired for two seconds and then AF inducibility was tested by whether activation was sustained for another second. ECGs and BSPMs were simulated. Equivalent atrial sources were extracted using second-order blind source separation, and their cycle length, periodicity and contribution, were used as features for random forest classifiers. Longer rotor duration during FS-driven episodes indicates higher AF inducibility (area under ROC curve = 0.83). Our method had accuracy of 90.6±1.0% and 90.6±0.6% in detecting FS presence, and 93.1±0.6% and 94.2±1.2% in identifying AF sustainability, and 80.0±6.6% and 61.0±5.2% in determining the atrium of the focal site, from BSPMs and ECGs of five atria. The detection of FS presence and AF sustainability were insensitive to vest placement (±9.6%). On pre-operative BSPMs of 52 paroxysmal AF patients, patients classified with initiator-type FS on a single atrium resulted in improved two-to-three-year AF-free likelihoods (p-value < 0.01, logrank tests). Detection of FS and arrhythmogenic substrate can be performed from ECGs and BSPMs, enabling non-invasive mapping towards mechanism-targeted AF treatment, and malignant ectopic beat detection with likely AF progression.

Background: Sole pulmonary vein (PV) isolation by ablation therapy prevents atrial fibrillation (AF) in patients with short episodes of AF and without comorbidities. Since incomplete PV isolation can be curative, we tested the hypothesis that the PV in the absence of remodeling and comorbidities contains structural and functional properties that are proarrhythmic for AF initiation by reentry.Methods: We performed percutaneous transvenous in vivo endocardial electrophysiological studies and quantitative histological analysis of PV from healthy sheep.Results: The proximal PV contained more myocytes than the distal PV and a higher percentage of collagen and fat tissue relative to myocytes than the left atrium. Local fractionated electrograms occurred in both the distal and proximal PVs, but a large local activation (>0.75 mV) was more often present in the proximal PV than in the distal PV (86 vs. 50% of electrograms, respectively, p = 0.017). Atrial arrhythmias (run of premature atrial complexes) occurred more often following the premature stimulation in the proximal PV than in the distal PV (p = 0.004). The diastolic stimulation threshold was higher in the proximal PV than in the distal PV (0.7 [0.3] vs. 0.4 [0.2] mA, (median [interquartile range]), p = 0.004). The refractory period was shorter in the proximal PV than in the distal PV (170 [50] vs. 248 [52] ms, p < 0.001). A linear relation existed between the gradient in refractoriness (distal-proximal) and atrial arrhythmia inducibility in the proximal PV.Conclusion: The structural and functional properties of the native atrial-PV junction differ from those of the distal PV. Atrial arrhythmias in the absence of arrhythmia-induced remodeling are caused by reentry in the atrial-PV junction. Ablative treatment of early paroxysmal AF, rather than complete isolation of focal arrhythmia, may be limited to inhibition of reentry.

Background: Because stretch of the atrial myocardium is proarrhythmic for atrial fibrillation (AF) and a left lateral body position increases atrial dimensions in humans, we hypothesized that left lateral recumbence is a frequent AF-triggering body position in AF patients.Methods: We performed a questionnaire study of symptomatic paroxysmal AF (episodes of AF < 1 week) patients scheduled for a first AF ablation therapy at Catharina Hospital, Eindhoven, the Netherlands and at University Hospital, Bordeaux, France.Results: Ninety-four symptomatic paroxysmal AF patients were included [mean age 61 ± 11 years, median AF history of 29(48) months, 31% were females]. Twenty-two percent of patients reported a specific body position as a trigger of their AF symptoms. The triggering body position was left lateral position in 57% of cases, supine position in 33%, right lateral position in 10%, and prone position in 5% (p = 0.003 overall difference in prevalence). Patients with positional AF had a higher body mass index compared to patients without nocturnal/positional AF [28.7(4.2) and 25.4(5.2) kg/m2, respectively, p = 0.025], but otherwise resembled these patients.Conclusion: Body position, and the left lateral position, in particular, is a common trigger of AF in symptomatic AF patients. Moreover, positional AF is associated with overweight. Understanding of the underlying mechanisms of positional AF can contribute to AF treatment and prevention.

Ablation of sites showing Purkinje activity is antiarrhythmic in some patients with idiopathic ventricular fibrillation (iVF). The mechanism for the therapeutic success of ablation is not fully understood. We propose that deeper penetrance of the Purkinje network allows faster activation of the ventricles and is proarrhythmic in the presence of steep repolarization gradients. Reduction of Purkinje penetrance, or its indirect reducing effect on apparent propagation velocity may be a therapeutic target in patients with iVF.

BackgroundVentricular fibrillation (VF) is the main cause of sudden cardiac death, but its mechanisms are still unclear. We propose a noninvasive approach to describe the progression of VF complexity from body surface potential maps (BSPMs).MethodsWe mapped 252 VF episodes (16 ± 10 s) with a 252-electrode vest in 110 patients (89 male, 47 ± 18 years): 50 terminated spontaneously, otherwise by electrical cardioversion (DCC). Changes in complexity were assessed between the onset (“VF start”) and the end (“VF end”) of VF by the nondipolar component index (NDIBSPM), measuring the fraction of energy nonpreserved by an equivalent 3D dipole from BSPMs. Higher NDI reflected lower VF organization. We also examined other standard body surface markers of VF dynamics, including fibrillatory wave amplitude (ABSPM), surface cycle length (BsCLBSPM) and Shannon entropy (ShEnBSPM). Differences between patients with and without structural heart diseases (SHD, 32 vs. NSHD, 78) were also tested at those stages. Electrocardiographic features were validated with simultaneous endocardium cycle length (CL) in a subset of 30 patients.ResultsAll BSPM markers measure an increase in electrical complexity during VF (p < 0.0001), and more significantly in NSHD patients. Complexity is significantly higher at the end of sustained VF episodes requiring DCC. Intraepisode intracardiac CL shortening (VF start 197 ± 24 vs. VF end 169 ± 20 ms; p < 0.0001) correlates with an increase in NDI, and decline in surface CL, f-wave amplitude, and entropy (p < 0.0001). In SHD patients VF is initially more complex than in NSHD patients (NDIBSPM, p = 0.0007; ShEnBSPM, p < 0.0001), with moderately slower (BsCLBSPM, p = 0.06), low-amplitude f-waves (ABSPM, p < 0.0001). In this population, lower NDI (p = 0.004) and slower surface CL (p = 0.008) at early stage of VF predict self-termination. In the NSHD group, a more abrupt increase in VF complexity is quantified by all BSPM parameters during sustained VF (p < 0.0001), whereas arrhythmia evolution is stable during self-terminating episodes, hinting at additional mechanisms driving VF dynamics.ConclusionMultilead BSPM analysis underlines distinct degrees of VF complexity based on substrate characteristics.

Evidence on sex differences in the pathophysiology and interventional treatment of ventricular arrhythmia in ischemic (ICM) or non-ischemic cardiomyopathies (NICM) is limited. However, women have different etiologies and types of structural heart disease due to sex differences in genetics, proteomics and sex hormones. These differences may influence ventricular electrophysiological parameters and may require different treatment strategies. Considering that women were consistently under-represented in all randomized-controlled trials on VT ablation, the applicability of the study results to female patients is not known. In this article, we review the current knowledge and gaps in evidence about sex differences in the epidemiology, pathophysiology and catheter ablation in patients with ventricular arrhythmias.

Background:SCN5A with Brugada syndrome (BrS) is not commonly considered as an independent risk marker for subsequent cardiac events. However, the risk of SCN5A combined with other clinical characteristics has not been fully investigated.Objectives: The aim of this study is to investigate and evaluate risk stratification and related risk factors of SCN5A in BrS.Methods: The databases of PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data were searched for related studies published from January 2002 to May 2018 followed by meta-analysis. The BrS patients who underwent SCN5A gene tests were included. The prognosis and risk stratification of SCN5A combined with symptoms and asymptoms diagnosis in BrS, electrophysiology study (EPS) were then investigated and evaluated. Outcomes were defined as ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD).Results: Eleven suitable studies involving 1892 BrS patients who underwent SCN5A gene tests were identified. SCN5A (+) was not considered to be a significant predictor of future cardiac events (95% CI: 0.89–2.11; P = 0.15; I2 = 0%). However, SCN5A (+) patients with symptoms at diagnosis revealed a higher prevalence of future VT/VF, SCD compared to SCN5A (–) patients with symptoms at diagnosis. (95% CI: 1.06–3.70; P = 0.03 I2 = 0%) Among asymptomatic patients, the risk did not significantly differ between SCN5A (+) patients and SCN5A (–) patients. (95% CI: 0.51–4.72; P = 0.45 I2 = 0 %). In an investigation involving patients in EPS (–) BrS electrocardiogram (ECG), the risk of SCN5A (+) is higher than that of SCN5A (–) (P < 0.001).Conclusions: In BrS patients with symptoms at diagnosis or EPS (–), the meta-analysis suggests that SCN5A (+) are at a higher risk of arrhythmic events than SCN5A (–).

An early repolarization pattern can be observed in 1% up to 13% of the overall population. Whereas, this pattern was associated with a benign outcome for many years, several more recent studies demonstrated an association between early repolarization and sudden cardiac death, so-called early repolarization syndrome. In early repolarization syndrome patients, current imbalances between epi- and endo-cardial layers result in dispersion of de- and repolarization. As a consequence, J waves or ST segment elevations can be observed on these patients' surface ECGs as manifestations of those current imbalances. Whereas, an early repolarization pattern is relatively frequently found on surface ECGs in the overall population, the majority of individuals presenting with an early repolarization pattern will remain asymptomatic and the isolated presence of an early repolarization pattern does not require further intervention. The mismatch between frequently found early repolarization patterns in the overall population, low incidences of sudden cardiac deaths related to early repolarization syndrome, but fatal, grave consequences in affected patients remains a clinical challenge. More precise tools for risk stratification and identification of this minority of patients, who will experience events, remain a clinical need. This review summarizes the epidemiologic, pathophysiologic and diagnostic background and presents therapeutic options of early repolarization syndrome.

Background: The use of surface recordings to assess atrial fibrillation (AF) complexity is still limited in clinical practice. We propose a noninvasive tool to quantify AF complexity from body surface potential maps (BSPMs) that could be used to choose patients who are eligible for AF ablation and assess therapy impact.Methods: BSPMs (mean duration: 7 ± 4 s) were recorded with a 252-lead vest in 97 persistent AF patients (80 male, 64 ± 11 years, duration 9.6 ± 10.4 months) before undergoing catheter ablation. Baseline cycle length (CL) was measured in the left atrial appendage. The procedural endpoint was AF termination. The ablation strategy impact was defined in terms of number of regions ablated, radiofrequency delivery time to achieve AF termination, and acute outcome. The atrial fibrillatory wave signal extracted from BSPMs was divided in 0.5-s consecutive segments, each projected on a 3D subspace determined through principal component analysis (PCA) in the current frame. We introduced the nondipolar component index (NDI) that quantifies the fraction of energy retained after subtracting an equivalent PCA dipolar approximation of heart electrical activity. AF complexity was assessed by the NDI averaged over the entire recording and compared to ablation strategy.Results: AF terminated in 77 patients (79%), whose baseline AF CL was 177 ± 40 ms, whereas it was 157 ± 26 ms in patients with unsuccessful ablation outcome (p = 0.0586). Mean radiofrequency emission duration was 35 ± 21 min; 4 ± 2 regions were targeted. Long-lasting AF patients (≥12 months) exhibited higher complexity, with higher NDI values (≥12 months: 0.12 ± 0.04 vs. 180 ms: 0.09 ± 0.03, p < 0.01). More organized AF as measured by lower NDI was associated with successful ablation outcome (termination: 0.10 ± 0.03 vs. no termination: 0.12 ± 0.04, p < 0.01), shorter procedures (

Alteration of action potential duration (APD) heterogeneity contributes to arrhythmogenesis. Purkinje-muscle junctions (PMJs) present differential electrophysiological properties including longer APD. The goal of this study was to determine if Purkinje-related or myocardial focal activation modulates ventricular repolarization differentially in healthy and ischemic myocardium. Simultaneous epicardial (EPI) and endocardial (ENDO) optical mapping was performed on sheep left ventricular (LV) wedges with intact free-running Purkinje network (N = 7). Preparations were paced on either ENDO or EPI surfaces, or the free-running Purkinje fibers (PFs), mimicking normal activation. EPI and ENDO APDs were assessed for each pacing configuration, before and after (7 min) of the onset of no-flow ischemia. Experiments were supported by simulations. In control conditions, maximal APD was found at endocardial PMJ sites. We observed a significant transmural APD gradient for PF pacing with PMJ APD = 347 ± 41 ms and EPI APD = 273 ± 36 ms (p < 0.001). A similar transmural gradient was observed when pacing ENDO (49 ± 31 ms; p = 0.005). However, the gradient was reduced when pacing EPI (37 ± 20 ms; p = 0.005). Global dispersion of repolarization was the most pronounced for EPI pacing. In ischemia, both ENDO and EPI APD were reduced (p = 0.005) and the transmural APD gradient (109 ± 55 ms) was increased when pacing ENDO compared to control condition or when pacing EPI (p < 0.05). APD maxima remained localized at functional PMJs during ischemia. Local repolarization dispersion was significantly higher at the PMJ than at other sites. The results were consistent with simulations. We found that the activation sequence modulates repolarization heterogeneity in the ischemic sheep LV. PMJs remain active following ischemia and exert significant influence on local repolarization patterns.

Electrocardiographic mapping (ECGI) detects reentrant drivers (RDs) that perpetuate arrhythmia in persistent AF (PsAF). Patient-specific computational models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) identify all latent sites in the fibrotic substrate that could potentially sustain RDs, not just those manifested during mapped AF. The objective of this study was to compare RDs from simulations and ECGI (RDsim/RDECGI) and analyze implications for ablation. We considered 12 PsAF patients who underwent RDECGI ablation. For the same cohort, we simulated AF and identified RDsim sites in patient-specific models with geometry and fibrosis distribution from pre-ablation LGE-MRI. RDsim- and RDECGI-harboring regions were compared, and the extent of agreement between macroscopic locations of RDs identified by simulations and ECGI was assessed. Effects of ablating RDECGI/RDsim were analyzed. RDsim were predicted in 28 atrial regions (median [inter-quartile range (IQR)] = 3.0 [1.0; 3.0] per model). ECGI detected 42 RDECGI-harboring regions (4.0 [2.0; 5.0] per patient). The number of regions with RDsim and RDECGI per individual was not significantly correlated (R = 0.46, P = ns). The overall rate of regional agreement was fair (modified Cohen's κ0 statistic = 0.11), as expected, based on the different mechanistic underpinning of RDsim- and RDECGI. nineteen regions were found to harbor both RDsim and RDECGI, suggesting that a subset of clinically observed RDs was fibrosis-mediated. The most frequent source of differences (23/32 regions) between the two modalities was the presence of RDECGI perpetuated by mechanisms other than the fibrotic substrate. In 6/12 patients, there was at least one region where a latent RD was observed in simulations but was not manifested during clinical mapping. Ablation of fibrosis-mediated RDECGI (i.e., targets in regions that also harbored RDsim) trended toward a higher rate of positive response compared to ablation of other RDECGI targets (57 vs. 41%, P = ns). Our analysis suggests that RDs in human PsAF are at least partially fibrosis-mediated. Substrate-based ablation combining simulations with ECGI could improve outcomes.

Much of our understanding of the mechanisms of macro re-entrant atrial tachycardia comes from study of cavotricuspid isthmus (CTI) dependent atrial flutter. In the majority of cases, the diagnosis can be made from simple analysis of the surface ECG. Endocardial mapping during tachycardia allows confirmation of the macro re-entrant circuit within the right atrium while, at the same time, permitting curative catheter ablation targeting the critical isthmus of tissue located between the tricuspid annulus and the inferior vena cava. The procedure is short, safe and by demonstration of an electrophysiological endpoint - bidirectional conduction block across the CTI - is associated with an excellent outcome following ablation. It is now fair to say that catheter ablation should be considered as a first line therapy for patients with documented CTI-dependent atrial flutter.

Abstract In the last three decades, ablation of atrial fibrillation (AF) has become an evidence‐based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society