Electrophysiologic Determinants of Isoelectric Intervals on Surface Electrocardiograms During Atrial Tachycardia: Insights From High-Density Mapping.

BACKGROUND: Substrate abnormalities can alter atrial activation during atrial tachycardias (ATs) thereby influencing AT-wave morphology on the surface electrocardiogram. OBJECTIVES: This study sought to identify determinants of isoelectric intervals during ATs with complex atrial activation patterns. METHODS: High-density activation maps of 126 ATs were studied. To assess the impact of the activated atrial surface on the presence of isoelectric intervals, this study measured the minimum activated area throughout the AT cycle, defined as the smallest activated area within a 50-millisecond period, by using signal processing algorithms (LUMIPOINT). RESULTS: ATs with isoelectric intervals (P-wave ATs) included 23 macro-re-entrant ATs (40%), 26 localized-re-entrant ATs (46%), and 8 focal ATs (14%), whereas those without included 46 macro-re-entrant ATs (67%), 21 localized-re-entrant ATs (30%), and 2 focal ATs (3%). Multivariable regression identified smaller minimum activated area and larger very low voltage area as independent predictors of P-wave ATs (OR: 0.732; 95% CI: 0.644-0.831; P < 0.001; and OR: 1.042; 95% CI: 1.006-1.080; P = 0.023, respectively). The minimum activated area with the cutoff value of 10 cm2 provided the highest predictive accuracy for P-wave ATs with sensitivity, specificity, and positive and negative predictive values of 96%, 97%, 97%, and 95%, respectively. In re-entrant ATs, smaller minimum activated area was associated with lower minimum conduction velocity within the circuit and fewer areas of delayed conduction outside of the circuit (standardized ß: 0.524; 95% CI: 0.373-0.675; P < 0.001; and standardized ß: 0.353; 95% CI: 0.198-0.508; P < 0.001, respectively). CONCLUSIONS: Reduced atrial activation area and voltage were associated with isoelectric intervals during ATs.

Abnormal Atrial Potentials Recorded During Sinus Rhythm or Pacing Represent Substrates for Reentrant Atrial Tachycardia.

BACKGROUND: Abnormal atrial potentials (AAPs) recorded during sinus rhythm/atrial pacing may indicate areas of slow conduction capable of supporting reentrant atrial tachycardia (AT). Therefore, we sought to examine the relationship between AAPs and AT circuits. METHODS: One hundred twenty-three reentrant ATs in 104 patients were analyzed. AAPs, consisting of fragmented potentials and split potentials, were assessed using the Rhythmia LUMIPOINT algorithm. RESULTS: There was 93±13% overlap between areas with AAPs during sinus rhythm/atrial pacing and areas of slow conduction along the reentry circuit during AT. The cumulative area of AAPs was smaller in patients with localized-reentrant ATs compared with anatomic macro-reentrant ATs (20.0 [14.6-30.5] versus 28.9 [21.8-35.6] cm2; P=0.021). Patients with perimitral ATs had larger areas of AAPs on the lateral wall whereas patients with roof-dependent ATs had larger areas of AAPs on the roof and posterior wall (P≤0.018 for all comparisons). The patchy scar that was associated with localized-reentrant AT exhibited a larger area of AAPs at its periphery than the scar that did not participate in localized-reentrant AT (3.1 [2.4-4.5] versus 1.0 [0.7-1.6] cm2; P<0.001). CONCLUSIONS: AAPs recorded during sinus rhythm/atrial pacing are associated with areas of slow conduction during reentrant AT. The burden and distribution of AAPs may provide actionable insights into AT circuit features, including in cases in which ATs are difficult to map.

Left Ventricular Abnormal Substrate in Brugada Syndrome.

BACKGROUND: Slow-conductive structural abnormalities located in the epicardium of the right ventricle (RV) underlie Brugada syndrome (BrS). The extent of such substrate in the left ventricle (LV) has not been investigated. OBJECTIVES: This study sought to characterize the extent of epicardial substrate abnormalities in BrS. METHODS: We evaluated 22 consecutive patients (mean age 46 ± 11 years, 21 male) referred for recurrent ventricular arrhythmias (mean 10 ± 13 episodes) in the setting of BrS. The patients underwent clinical investigations and wide genetic screening to identify SCN5A mutations and common risk variants. High-density biventricular epicardial mapping was performed to detect prolonged (>70 ms) fragmented electrograms, indicating abnormal substrate area. RESULTS: All patients presented with abnormal substrate in the epicardial anterior RV (27 ± 11 cm2). Abnormal substrate was also identified on the LV epicardium in 10 patients (45%), 9 at baseline and 1 after ajmaline infusion, covering 15 ± 11 cm2. Of these, 4 had severe LV fascicular blocks. Patients with LV substrate had a longer history of arrhythmia (11.4 ± 6.7 years vs 4.3 ± 4.3 years; P = 0.003), longer PR (217 ± 24 ms vs 171 ± 14 ms; P < 0.001) and HV (60 ± 12 ms vs 46 ± 5 ms; P = 0.005) intervals, and abnormal substrate also extending into the inferior RV (100% vs 33%; P = 0.001). SCN5A mutation was present in 70% of patients with LV substrate (vs 25%; P = 0.035). SCN5A BrS patients with recurrent ventricular arrhythmias present a higher polygenic risk score compared with a nonselected BrS population (median of differences: -0.86; 95% CI: -1.48 to -0.27; P = 0.02). CONCLUSIONS: A subset of patients with BrS present an abnormal substrate extending onto the LV epicardium and inferior RV that is associated with SCN5A mutations and multigenic variants.

Impact of filter configurations on bipolar EGMs: An optimal filter setting for identifying VT substrates.

BACKGROUND: The impact of filtering on bipolar electrograms (EGMs) has not been systematically examined. We tried to clarify the optimal filter configuration for ventricular tachycardia (VT) ablation. METHODS: Fifteen patients with VT were included. Eight different filter configurations were prospectively created for the distal bipoles of the ablation catheter: 1.0-250, 10-250, 100-250, 30-50, 30-100, 30-250, 30-500, and 30-1000 Hz. Pre-ablation stable EGMs with good contact (contact force > 10 g) were analyzed. Baseline fluctuation, baseline noise, bipolar peak-to-peak voltage, and presence of local abnormal ventricular activity (LAVA) were compared between different filter configurations. RESULTS: In total, 2276 EGMs with multiple bipolar configurations in 246 sites in scar and border areas were analyzed. Baseline fluctuation was only observed in the high-pass filter of (HPF) ≤ 10 Hz (p < .001). Noise level was lowest at 30-50 Hz (0.018 [0.012-0.029] mV), increased as the low-pass filter (LPF) extended, and was highest at 30-1000 Hz (0.047 [0.041-0.061] mV) (p < .001). Conversely, the HPF did not affect the noise level at ≤30 Hz. As the HPF extended to 100 Hz, bipolar voltages significantly decreased (p < .001), but were not affected when the LPF was extended to ≥100 Hz. LAVAs were most frequently detected at 30-250 Hz (207/246; 84.2%) and 30-500 Hz (208/246; 84.6%), followed by 30-1000 Hz (205/246; 83.3%), but frequently missed at LPF ≤ 100 Hz or HPF ≤ 10 Hz (p < .001). A 50-Hz notch-filter reduced the bipolar voltage by 43.9% and LAVA-detection by 34.5% (p < .0001). CONCLUSION: Bipolar EGMs are strongly affected by filter settings in scar/border areas. In all, 30-250 or 30-500 Hz may be the best configuration, minimizing the baseline fluctuation, baseline noise, and detecting LAVAs. Not applying the 50-Hz notch filter may be beneficial to avoid missing VT substrate.

Detailed analysis of tachycardia cycle length aids diagnosis of the mechanism and location of atrial tachycardias.

AIMS: Although the mechanism of an atrial tachycardia (AT) can usually be elucidated using modern high-resolution mapping systems, it would be helpful if the AT mechanism and circuit could be predicted before initiating mapping. OBJECTIVE: We examined if the information gathered from the cycle length (CL) of the tachycardia can help predict the AT-mechanism and its localization. METHODS: One hundred and thirty-eight activation maps of ATs including eight focal-ATs, 94 macroreentrant-ATs, and 36 localized-ATs in 95 patients were retrospectively reviewed. Maximal CL (MCL) and minimal CL (mCL) over a minute period were measured via a decapolar catheter in the coronary sinus. CL-variation and beat-by-beat CL-alternation were examined. Additionally, the CL-respiration correlation was analysed by the RhythmiaTM system. : Both MCL and mCL were significantly shorter in macroreentrant-ATs [MCL = 288 (253-348) ms, P = 0.0001; mCL = 283 (243-341) ms, P = 0.0012], and also shorter in localized-ATs [MCL = 314 (261-349) ms, P = 0.0016; mCL = 295 (248-340) ms, P = 0.0047] compared to focal-ATs [MCL = 506 (421-555) ms, mCL = 427 (347-508) ms]. An absolute CL-variation (MCL-mCL) < 24 ms significantly differentiated re-entrant ATs from focal-ATs with a sensitivity = 96.9%, specificity = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 66.7%. The beat-by-beat CL-alternation was observed in 10/138 (7.2%), all of which showed the re-entrant mechanism, meaning that beat-by-beat CL-alternation was the strong sign of re-entrant mechanism (PPV = 100%). Although the CL-respiration correlation was observed in 28/138 (20.3%) of ATs, this was predominantly in right-atrium (RA)-ATs (24/41, 85.7%), rather than left atrium (LA)-ATs (4/97, 4.1%). A positive CL-respiration correlation highly predicted RA-ATs (PPV = 85.7%), and negative CL-respiration correlation probably suggested LA-ATs (NPV = 84.5%). CONCLUSION: Detailed analysis of the tachycardia CL helps predict the AT-mechanism and the active AT chamber before an initial mapping.

Electrophysiological study prior to planned pulmonary valve replacement in patients with repaired tetralogy of Fallot.

AIM: Ventricular arrhythmias (VAs) are the most common cause of death in patients with repaired Tetralogy of Fallot (rTOF). However, risk stratifying remains challenging. We examined outcomes following programmed ventricular stimulation (PVS) with or without subsequent ablation in patients with rTOF planned for pulmonary valve replacement (PVR). METHODS: We included all consecutive patients with rTOF referred to our institution from 2010 to 2018 aged ≥18 years for PVR. Right ventricular (RV) voltage maps were acquired and PVS was performed from two different sites at baseline, and if non-inducible under isoproterenol. Catheter and/or surgical ablation was performed when patients were inducible or when slow conduction was present in anatomical isthmuses (AIs). Postablation PVS was undertaken to guide implantable cardioverter-defibrillator (ICD) implantation. RESULTS: Seventy-seven patients (36.2 ± 14.3 years old, 71% male) were included. Eighteen were inducible. In 28 patients (17 inducible, 11 non-inducible but with slow conduction) ablation was performed. Five had catheter ablation, surgical cryoablation in 9, both techniques in 14. ICDs were implanted in five patients. During a follow-up of 74 ± 40 months, no sudden cardiac death occurred. Three patients experienced sustained VAs, all were inducible during the initial EP study. Two of them had an ICD (low ejection fraction for one and important risk factor for arrhythmia for the second). No VAs were reported in the non-inducible group (p < .001). CONCLUSION: Preoperative EPS can help identifying patients with rTOF at risk for VAs, providing an opportunity for targeted ablation and may improve decision-making regarding ICD implantation.

High-resolution mapping of reentrant atrial tachycardias: Relevance of low bipolar voltage.

BACKGROUND: Bipolar voltage is widely used to characterize the atrial substrate but has been poorly validated, particularly during clinical tachycardias. OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of voltage thresholds for identifying regions of slow conduction during reentrant atrial tachycardias (ATs). METHODS: Thirty bipolar voltage and activation maps created during reentrant ATs were analyzed to (1) examine the relationship between voltage amplitude and conduction velocity (CV), (2) measure the diagnostic ability of voltage thresholds to predict CV, and (3) identify determinants of AT circuit dimensions. Voltage amplitude was categorized as "normal" (>0.50 mV), "abnormal" (0.05-0.50 mV), or "scar" (<0.05 mV); slow conduction was defined as <30 cm/s. RESULTS: A total of 266,457 corresponding voltage and CV data points were included for analysis. Voltage and CV were moderately correlated (r = 0.407; P < .001). Bipolar voltage predicted regions of slow conduction with an area under the receiver operating characteristic curve of 0.733 (95% confidence interval 0.731-0.735). A threshold of 0.50 mV had 91% sensitivity and 35% specificity for identifying slow conduction, whereas 0.05 mV had 36% sensitivity and 87% specificity, with an optimal voltage threshold of 0.15 mV. Analyses restricted to the AT circuits identified weaker associations between voltage and CV and an optimal voltage threshold of 0.25 mV. CONCLUSION: Widely used bipolar voltage amplitude thresholds to define "abnormal" and "scar" tissue in the atria are, respectively, sensitive and specific for identifying regions of slow conduction during reentrant ATs. However, overall, the association of voltage with CV is modest. No clinical predictors of AT circuit dimensions were identified.

Gaps after linear ablation of persistent atrial fibrillation (Marshall-PLAN): Clinical implication.

BACKGROUND: Beyond pulmonary vein (PV) isolation, anatomic isthmus transection is an adjunctive strategy for persistent atrial fibrillation. Data on the durability of multiple lines of block remain scarce. OBJECTIVE: The purpose of this study was to evaluate the impact of gaps within such a lesion set. METHODS: We followed 291 consecutive patients who underwent (1) vein of Marshall ethanol infusion, (2) PV isolation, and (3) mitral, cavotricuspid, and dome isthmus transection. Dome transection relied on 2 distinct strategies over time: a single roof line with touch-ups applied in case of gap demonstrated by conventional maneuvers (first leg), and an alternative floor line if the roof line exhibited a gap during high-density mapping with careful electrogram reannotation (second leg). RESULTS: Twelve-month sinus rhythm maintenance was 70% after 1 procedure and 94% after 1 or 2 procedures. Event-free survival after the first procedure was lower in case of residual gaps within the lesion set (log-rank, P = .004). Delayed gaps were found in 94% of a second procedure performed in the 69 patients relapsing despite a complete lesion set with PV gaps increasing the risk of recurrence of atrial fibrillation (67% vs 34%; P = .02) and anatomic isthmus gaps supporting a majority of atrial tachycardias (60%). Between the first leg and the second leg, a significant decrease was found in roof lines considered blocked during the first procedure (99% vs 78%; P < .001) and in delayed dome gaps observed during a second procedure (68% vs 43%; P = .05). CONCLUSION: Gaps are arrhythmogenic and can be reduced by optimized ablation and assessment of lines of block. Closing these gaps improves sinus rhythm maintenance.

Malignant Purkinje ectopy induced by sodium channel blockers.

BACKGROUND: Sodium channel blocker (SCB) infusion is used to unmask the electrocardiographic pattern of Brugada syndrome. The test may also induce premature ventricular complexes (PVCs) in individuals without Brugada pattern, the clinical relevance of which is little known. OBJECTIVE: The purpose of this study was to describe the prevalence of short-coupled (Sc) PVCs induced by ajmaline or flecainide in patients with suspected or documented severe ventricular arrhythmias. METHODS: We reviewed the SCB tests performed in 335 patients with suspected ventricular arrhythmias and structurally normal hearts in 9 centers. ScPVCs were defined as frequent and repetitive PVCs with an R-on-T pattern on SCB tests. Repeated SCB tests were performed in 7 patients and electrophysiological mapping of ScPVCs in 9. RESULTS: Sixteen patients (8 men; mean age 36 ± 11 years) showed ScPVCs and were included. ScPVCs appeared 229 ± 118 seconds after the initiation of infusion and displayed coupling intervals of 288 ± 28 ms. ScPVC patterns were monomorphic in 12 patients, originating from the Purkinje system in mapped patients. Repetitive PVCs were induced in 15 patients (94%) including polymorphic ventricular tachycardias in 9 (56%). SCB infusion was repeated 45 (interquartile range 0.6-46) months later and induced identical ScPVC in all. SCB test was the only mean to reveal the malignant arrhythmia in 6 patients. Catheter ablation was performed in 9 patients, resulting in arrhythmia elimination in 8 with a follow-up of 6 (interquartile range 2-9) years. CONCLUSION: SCB can induce ScPVC, mostly from Purkinje tissue, in a small subset of patients with idiopathic ventricular arrhythmias. Its high reproducibility suggests a distinct individual mechanism.

Distribution of atrial low voltage induced by vein of Marshall ethanol infusion.

INTRODUCTION: Systematic and quantitative descriptions of vein of Marshall (VOM)-induced tissue ablation are lacking. We sought to characterize the distribution of low voltage observed in the left atrium (LA) after VOM ethanol infusion. METHODS AND RESULTS: The distribution of ethanol-induced low voltage was evaluated by comparing high-density maps performed before and after VOM ethanol infusion in 114 patients referred for atrial fibrillation ablation. The two most frequently impacted segments were the inferior portion of the ridge (82.5%) and the first half of the mitral isthmus (pulmonary vein side) (92.1%). Low-voltage absence in these typical areas resulted from inadvertent ethanol infusion in the left atrial appendage vein (n = 3), initial VOM dissection (n = 3), or a "no branches" VOM morphology (n = 1). Visible anastomosis of the VOM with roof or posterior veins more frequently resulted in low-voltage extension beyond typical areas, toward the entire left antrum (19.0% vs. 1.9%, p = .0045) or the posterior LA (39.7% vs. 3.8%, p < .001) but with a limited positive predictive value ranging from 29.4% to 43.5%. Ethanol-induced low voltage covered a median LA surface of 3.6% (1.9%-5.0%) and did not exceed 8% of the LA surface in 90% of patients. CONCLUSION: VOM ethanol infusion typically locates at the inferior ridge and the adjacent half of the mitral isthmus. Low-voltage extensions can be anticipated but not guaranteed by the presence of visible anastomosis of the VOM with roof or posterior veins.

Preoperative personalization of atrial fibrillation ablation strategy to prevent esophageal injury: Impact of changes in esophageal position.

INTRODUCTION: Due to changes in esophageal position, preoperative assessment of the esophageal location may not mitigate the risk of esophageal injury in catheter ablation for atrial fibrillation (AF). This study aimed to assess esophageal motion and its impact on AF ablation strategies. METHODS AND RESULTS: Ninety-seven AF patients underwent two computed tomography (CT) scans. The area at risk of esophageal injury (AAR) was defined as the left atrial surface ≤3 mm from the esophagus. On CT1, ablation lines were drawn blinded to the esophageal location to create three ablation sets: individual pulmonary vein isolation (PVI), wide antral circumferential ablation (WACA), and WACA with linear ablation (WACA + L). Thereafter, ablation lines for WACA and WACA + L were personalized to avoid the AAR. Rigid registration was performed to align CT1 onto CT2, and the relationship between ablation lines and the AAR on CT2 was analyzed. The esophagus moved by 3.6 [2.7 to 5.5] mm. The AAR on CT2 was 8.6 ± 3.3 cm2 , with 77% overlapping that on CT1. High body mass index was associated with the AAR mismatch (standardized ß 0.382, p < .001). Without personalization, AARs on ablation lines for individual PVI, WACA, and WACA + L were 0 [0-0.4], 0.8 [0.5-1.2], and 1.7 [1.2-2.0] cm2 . Despite the esophageal position change, the personalization of ablation lines for WACA and WACA + L reduced the AAR on lines to 0 [0-0.5] and 0.7 [0.3-1.0] cm2 (p < .001 for both). CONCLUSION: The personalization of ablation lines based on a preoperative CT reduced ablation to the AAR despite changes in esophageal position.

Strategy for repeat procedures in patients with persistent atrial fibrillation: Systematic linear ablation with adjunctive ethanol infusion into the vein of Marshall versus electrophysiology-guided ablation.

INTRODUCTION: The optimal strategy after a failed ablation for persistent atrial fibrillation (perAF) is unknown. This study evaluated the value of an anatomically guided strategy using a systematic set of linear lesions with adjunctive ethanol infusion into the vein of Marshall (Et-VOM) in patients referred for second perAF ablation procedures. METHODS AND RESULTS: Patients with perAF who underwent a second procedure were grouped according to the two strategies. The first strategy was an anatomically guided approach using systematic linear ablation with adjunctive Et-VOM, with bidirectional blocks at the posterior mitral isthmus (MI), roof, and cavotricuspid isthmus (CTI) as the procedural endpoint (Group I). The second one was an electrophysiology-guided strategy, with atrial tachyarrhythmia termination as the procedural endpoint (Group II). Arrhythmia behavior during the procedure guided the ablation strategy. Groups I and II consisted of 96 patients (65 ± 9 years; 71 men) and 102 patients (63 ± 10 years; 83 men), respectively. Baseline characteristics were comparable. In Group I, Et-VOM was successfully performed in 91/96 (95%), and procedural endpoint (bidirectional block across all three anatomical lines) was achieved in 89/96 (93%). In Group II, procedural endpoint (atrial tachyarrhythmia termination) was achieved in 80/102 (78%). One-year follow-up demonstrated Group I (21/96 [22%]) experienced less recurrence compared to Group II (38/102 [37%], Log-rank p = .01). This was driven by lower AT recurrence in Group I (Group I: 10/96 [10%] vs. Group II: 29/102 [28%]; p = .002). CONCLUSION: Anatomically guided strategy with adjunctive Et-VOM is superior to an electrophysiology-guided strategy for second procedures in patients with perAF at 1-year follow-up.

Optimized Computed Tomography Acquisition Protocol for Ethanol Infusion Into the Vein of Marshall.

OBJECTIVES: This study sought to introduce a computed tomography (CT) protocol for optimal planning of vein of Marshall (VOM) catheterization. BACKGROUND: Ethanol infusion into the VOM (Et-VOM) is increasingly used in atrial fibrillation ablation. METHODS: Preprocedural CT was performed with either a conventional (conv-CT; n = 132) or an optimized CT protocol (VOM-CT; n = 126) designed for obtaining on a single image both left atrial and coronary sinus (CS) enhancement. The detection rate and anatomical features of the CT-derived VOM were analyzed and the utility of VOM-CT protocol was assessed by comparing the procedural data. RESULTS: VOM was detected in 35% in conv-CT versus 63% in VOM-CT (P < 0.001). The VOM-CT protocol did not impair the assessment of left atrial anatomy and appendage patency. In VOM-CT, the detection of the VOM was related to body mass index and width of epicardial space on posterior wall. Mean distance between CS ostium and VOM was 36 ± 7 mm. Mean VOM diameter was 1.6 ± 0.3 mm. On the CS circumference, the VOM emerged superiorly in 68% and postero-superiorly in 32%. Ethanol infusion into the VOM was attempted in 165 patients (77 conv-CT, 70 VOM-CT, and 18 without-CT). After registration in CARTO, the VOM segmented on CT matched its location on venography in all cases. As compared with conv-CT and without-CT, procedures guided by VOM-CT showed significantly shorter radiation time, shorter procedure time, lower amount of the contrast medium, and fewer contrast injections to obtain VOM catheterization. CONCLUSIONS: The proposed CT protocol allows for improved visualization of the VOM, translating into easier VOM catheterization.

Purkinje network and myocardial substrate at the onset of human ventricular fibrillation: implications for catheter ablation.

AIMS: Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with structural cardiac abnormalities. METHODS AND RESULTS: We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes [interquartile range (IQR) 4-16] to 0 episode (IQR 0-2) (P < 0.001) at 56 ± 30 months. CONCLUSIONS: The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden. KEY QUESTION: The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown. KEY FINDING: Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients. TAKE-HOME MESSAGE: The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.

Sinus node exit, crista terminalis conduction, interatrial connection, and wavefront collision: Key features of human atrial activation in sinus rhythm.

BACKGROUND: An understanding of normal atrial activation during sinus rhythm can inform catheter ablation strategies to avoid deleterious impacts of ablation lesions on atrial conduction and mechanics. OBJECTIVE: The purpose of this study was to describe how the sinus node impulse originates, propagates, and collides in right and left atria with normal voltage. METHODS: Fifty consecutive patients undergoing catheter ablation of atrial fibrillation with endocardial atrial voltage >0.5 mV during high-density 3-dimensional mapping were studied. RESULTS: Sinus node exits varied among patients along a lateral oblique arc extending from the anterior aspect of the superior vena cava (SVC) to the mid-posterior wall of the right atrium (RA). Conduction slowing or block at one of the smooth components that faces the crista terminalis was observed in 54% of cases, including complete block at the SVC musculature and systemic venous sinus in 6% of cases. Depending on these 2 key features of RA activation, interatrial conduction was mediated by the Bachmann bundle (64%) and posterior bundles (54%), with an overlap of the resulting left atrial breakthrough location. Wavefront collision was consistently observed at 3 sites: the septal aspect of the cavotricuspid isthmus, and the lower aspects of the dome and of the mitral isthmus. CONCLUSION: During sinus rhythm, atrial activation occurs via distinct sequences mediated by a complex interaction of anatomic factors.