Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry.

BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

3D mapping of phrenic nerve course for radiofrequency pulmonary vein isolation.

INTRODUCTION: Phrenic nerve (PN) injury is a rare but severe complication of radiofrequency (RF) pulmonary vein isolation (PVI). The objective of this study was to characterize the typical intracardiac course of the PN with a three-dimensional electroanatomic mapping system, to quantify the need for modification of the ablation trajectory to avoid delivering an ablation lesion on sites with PN capture, and to identify very circumscribed areas of common PNC on the routine ablation trajectory of a RF-PVI, allowing fast and effective PN screening for everyday usage. METHODS: We enrolled 137 consecutive patients (63 ± 9 years, 64% men) undergoing PVI. A detailed high output (20 mA) pace-mapping protocol was performed in the right (RA) and left atrium (LA) and adjacent vasculature. RESULTS: The right PN was most commonly captured in the superior vena cava at a lateral (50%) or posterolateral (23%) position before descending along the RA either straight (29%) or with a posterolateral bend (20%). In the LA, beginning deep within the right superior pulmonary vein (RSPV), the right PN is most frequently detectable anterolateral (31%), then descends to the lateral proximal RSPV (23%), and further towards the lateral antral region (15%) onto the medial LA wall (12%). To avoid delivering an ablation lesion on sites with PN capture, modification of ablation trajectory was necessary in 23% of cases, most commonly in the lateral RSPV antrum (81%). No PN injury occurred. CONCLUSION: PN mapping frequently reveals the close proximity of the PN to the ablation trajectory during PVI, particularly in the lateral RSPV antrum. Routine PN pacing should be considered during RF PVI procedures.

Spatial correlation of left atrial low voltage substrate in sinus rhythm versus atrial fibrillation: The rhythm specificity of atrial low voltage substrate.

INTRODUCTION: Improved sinus rhythm (SR) maintenance rates have been achieved in patients with persistent atrial fibrillation (AF) undergoing pulmonary vein isolation plus additional ablation of low voltage substrate (LVS) during SR. However, voltage mapping during SR may be hindered in persistent and long-persistent AF patients by immediate AF recurrence after electrical cardioversion. We assess correlations between LVS extent and location during SR and AF, aiming to identify regional voltage thresholds for rhythm-independent delineation/detection of LVS areas. (1) Identification of voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm substrate detection. (3) Comparison of LVS between SR and native versus induced AF. METHODS: Forty-one ablation-naive persistent AF patients underwent high-definition (1 mm electrodes; >1200 left atrial (LA) mapping sites per rhythm) voltage mapping in SR and AF. Global and regional voltage thresholds in AF were identified which best match LVS < 0.5 mV and <1.0 mV in SR. Additionally, the correlation between SR-LVS with induced versus native AF-LVS was assessed. RESULTS: Substantial voltage differences (median: 0.52, interquartile range: 0.33-0.69, maximum: 1.19 mV) with a predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34 mV for the entire left atrium provides an accuracy, sensitivity and specificity of 69%, 67%, and 69% to identify SR-LVS < 0.5 mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3 mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (area under the curve[AUC]: 0.80 vs. 0.73). AF-LVS < 0.5 mV corresponds to SR-LVS < 0.97 mV (AUC: 0.73). CONCLUSION: Although the proposed region-specific voltage thresholds during AF improve the consistency of LVS identification as determined during SR, the concordance in LVS between SR and AF remains moderate, with larger LVS detection during AF. Voltage-based substrate ablation should preferentially be performed during SR to limit the amount of ablated atrial myocardium.

Characterization of circumferential antral pulmonary vein isolation areas resulting from pulsed-field catheter ablation.

AIMS: The cornerstone of pulmonary vein (PV) isolation (PVI) is a wide-area circumferential ablation (WACA) resulting in an antral PVI area. Pulsed-field ablation (PFA) is a new nonthermal 'single-shot' PVI technique resulting in well-characterized posterior isolation areas. However, information on circumferential PVI area is lacking. Thus, we sought to characterize the circumferential antral PVI areas after PFA-PVI. METHODS AND RESULTS: Atrial fibrillation (AF) patients underwent fluoroscopy-guided PVI with a pentaspline PFA catheter. Ultra-high-density voltage maps using a 20-polar circular mapping catheter were created before and immediately after PVI to identify and quantify (i) insufficient isolation areas per antral PV segment (10-segment model) and (ii) enlarged left atrial (LA) isolation areas (beyond the antral PV segments) per LA region (8-region model). The PFA-PVI with pre- (5469 ± 1822 points) and post-mapping (6809 ± 2769 points) was performed in 40 consecutive patients [age 62 ± 6 years, 25/40 (62.5%) paroxysmal AF]. Insufficient isolation areas were located most frequently in the anterior antral PV segments of the left PVs (62.5-77.5% of patients) with the largest extent (median ≥0.4 cm2) located in the same segments (segments 2/5/8). Enlarged LA isolation areas were located most frequently and most extensively on the posterior wall and roof region (89.5-100% of patients; median 1.1-2.7 cm2 per region). CONCLUSION: Fluoroscopy-guided PFA-PVI frequently results in insufficient isolation areas in the left anterior antral PV segments and enlarged LA isolation areas on the posterior wall/roof, which both may be extensive. To optimize the procedure, full integration of PFA catheter visualization into three-dimensional-mapping systems is needed.

Feasibility and safety of a three-dimensional anatomic map-guided transseptal puncture for left-sided catheter ablation procedures.

AIMS: Transseptal puncture (TP) for left-sided catheter ablation procedures is routinely performed under fluoroscopic or echocardiographic guidance [transoesophageal echocardiography (TEE) or intracardiac echocardiography (ICE)], although three-dimensional (3D) mapping systems are readily available in most electrophysiology laboratories. Here, we sought to assess the feasibility and safety of a right atrial (RA) 3D map-guided TP. METHODS AND RESULTS: In 104 patients, 3D RA mapping was performed to identify the fossa ovalis (FO) using the protrusion technique. The radiofrequency transseptal needle was visualized and navigated to the desired potential FO-TP site. Thereafter, the interventionalist was unblinded to TEE and the potential FO-TP site was reassessed regarding its convenience and safety. After TP, the exact TP site was documented using a 17-segment-FO model. Reliable identification of the FO was feasible in 102 patients (98%). In these, 114 3D map-guided TP attempts were performed, of which 96 (84%) patients demonstrated a good position and 18 (16%) an adequate position after TEE unblinding. An out-of-FO or dangerous position did not occur. A successful 3D map-guided TP was performed in 110 attempts (97%). Four attempts (3%) with adequate positions were aborted in order to seek a more convenient TP site. The median time from RA mapping until the end of the TP process was 13 (12-17) min. No TP-related complications occurred. Ninety-eight TP sites (85.1%) were in the central portion or in the inner loop of the FO. CONCLUSION: A 3D map-guided TP is feasible and safe. It may assist to decrease radiation exposure and the need for TEE/ICE during left-sided catheter ablation procedures.

Differences in atrial substrate localization using late gadolinium enhancement-magnetic resonance imaging, electrogram voltage, and conduction velocity: a cohort study using a consistent anatomical reference frame in patients with persistent atrial fibrillation.

AIMS: Electro-anatomical voltage, conduction velocity (CV) mapping, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) have been correlated with atrial cardiomyopathy (ACM). However, the comparability between these modalities remains unclear. This study aims to (i) compare pathological substrate extent and location between current modalities, (ii) establish spatial histograms in a cohort, (iii) develop a new estimated optimized image intensity threshold (EOIIT) for LGE-MRI identifying patients with ACM, (iv) predict rhythm outcome after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF). METHODS AND RESULTS: Thirty-six ablation-naive persistent AF patients underwent LGE-MRI and high-definition electro-anatomical mapping in sinus rhythm. Late gadolinium enhancement areas were classified using the UTAH, image intensity ratio (IIR >1.20), and new EOIIT method for comparison to low-voltage substrate (LVS) and slow conduction areas <0.2 m/s. Receiver operating characteristic analysis was used to determine LGE thresholds optimally matching LVS. Atrial cardiomyopathy was defined as LVS extent ≥5% of the left atrium (LA) surface at <0.5 mV. The degree and distribution of detected pathological substrate (percentage of individual LA surface are) varied significantly (P < 0.001) across the mapping modalities: 10% (interquartile range 0-14%) of the LA displayed LVS <0.5 mV vs. 7% (0-12%) slow conduction areas <0.2 m/s vs. 15% (8-23%) LGE with the UTAH method vs. 13% (2-23%) using IIR >1.20, with most discrepancies on the posterior LA. Optimized image intensity thresholds and each patient's mean blood pool intensity correlated linearly (R2 = 0.89, P < 0.001). Concordance between LGE-MRI-based and LVS-based ACM diagnosis improved with the novel EOIIT applied at the anterior LA [83% sensitivity, 79% specificity, area under the curve (AUC): 0.89] in comparison to the UTAH method (67% sensitivity, 75% specificity, AUC: 0.81) and IIR >1.20 (75% sensitivity, 62% specificity, AUC: 0.67). CONCLUSION: Discordances in detected pathological substrate exist between LVS, CV, and LGE-MRI in the LA, irrespective of the LGE detection method. The new EOIIT method improves concordance of LGE-MRI-based ACM diagnosis with LVS in ablation-naive AF patients but discrepancy remains particularly on the posterior wall. All methods may enable the prediction of rhythm outcomes after PVI in patients with persistent AF.

Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF). METHODS AND RESULTS: In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03-93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively. CONCLUSION: Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AIMS: Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS: This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION: In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement.

Easily available ECG and echocardiographic parameters for prediction of left atrial remodeling and atrial fibrillation recurrence after pulmonary vein isolation: A multicenter study.

BACKGROUND: The assessment of noninvasive markers of left atrial (LA) low-voltage substrate (LVS) enables the identification of atrial fibrillation (AF) patients at risk for arrhythmia recurrence after pulmonary vein isolation (PVI). METHODS: In this prospective multicenter study, 292 consecutive AF patients (72% male, 62 ± 11 years, 65% persistent AF) underwent high-density LA voltage mapping in sinus rhythm. LA-LVS (<0.5 mV) was considered as significant at 2 cm2  or above. Preprocedural clinical electrocardiogram and echocardiographic data were assessed to identify predictors of LA-LVS. The role of the identified LA-LVS markers in predicting 1-year arrhythmia freedom after PVI was assessed in 245 patients. RESULTS: Significant LA-LVS was identified in 123 (42%) patients. The amplified sinus P-wave duration (APWD) best predicted LA-LVS, with a 148-ms value providing the best-balanced sensitivity (0.81) and specificity (0.88). An APWD over 160 ms was associated with LA-LVS in 96% of patients, whereas an APWD under 145 ms in 15%. Remaining gray zones improved their accuracy by introduction of systolic pulmonary artery pressure (sPAP) of 35 mmHg or above, age, and sex. According to COX regression, the risk of arrhythmia recurrence 12 months following PVI was twofold and threefold higher in patients with APWD 145-160 and over 160 ms, compared to APWD under 145 ms. Integration of pulmonary hypertension further improved the outcome prediction in the intermediate APWD group: Patients with APWD 145-160 ms and normal sPAP had similar outcome than patients with APWD under 145 ms (hazard ratio [HR] 1.62, p = .14), whereas high sPAP implied worse outcome (HR 2.56, p < .001). CONCLUSIONS: The APWD identifies LA-LVS and risk for arrhythmia recurrence after PVI. Our prediction model becomes optimized by means of integration of the pulmonary artery pressure.

Non-invasive body surface electrocardiographic imaging for diagnosis of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with new-onset atrial fibrillation, arrhythmia recurrence after pulmonary vein isolation (PVI) and increased risk for stroke. At present, diagnosis of ACM is feasible by endocardial contact mapping of left atrial (LA) low-voltage substrate (LVS) or late gadolinium-enhanced magnetic resonance imaging, but their complexity limits a widespread use. The aim of this study was to assess non-invasive body surface electrocardiographic imaging (ECGI) as a novel clinical tool for diagnosis of ACM compared with endocardial mapping. METHODS AND RESULTS: Thirty-nine consecutive patients (66 ± 9 years, 85% male) presenting for their first PVI for persistent atrial fibrillation underwent ECGI in sinus rhythm using a 252-electrode-array mapping system. Subsequently, high-density LA voltage and biatrial activation maps (mean 2090 ± 488 sites) were acquired in sinus rhythm prior to PVI. Freedom from arrhythmia recurrence was assessed within 12 months follow-up. Increased duration of total atrial conduction time (TACT) in ECGI was associated with both increased atrial activation time and extent of LA-LVS in endocardial contact mapping (r = 0.77 and r = 0.66, P < 0.0001 respectively). Atrial cardiomyopathy was found in 23 (59%) patients. A TACT value of 148 ms identified ACM with 91.3% sensitivity and 93.7% specificity. Arrhythmia recurrence occurred in 15 (38%) patients during a follow-up of 389 ± 55 days. Freedom from arrhythmia was significantly higher in patients with a TACT <148 ms compared with patients with a TACT ≥148 ms (82.4% vs. 45.5%, P = 0.019). CONCLUSION: Analysis of TACT in non-invasive ECGI allows diagnosis of patients with ACM, which is associated with a significantly increased risk for arrhythmia recurrence following PVI.

Effect of a restrictive pacemaker implantation strategy on mortality after transcatheter aortic valve implantation.

OBJECTIVES: We sought to assess the safety of a restrictive permanent pacemaker implantation (PPI) strategy after transcatheter aortic valve implantation (TAVI) as compared to a liberal strategy. BACKGROUND: Conduction disturbances resulting in PPI are common after TAVI. However, conduction disturbances may be transient and PPI may be superfluous in some patients. METHODS: Until August 2015, we performed PPI in all patients with new complete left bundle branch block (LBBB, QRS > 120 milliseconds) or higher degree atrioventricular (AV) blocks (liberal strategy). From September 2015 onwards, LBBB established an indication for PPI only in the presence of new-onset AV block (PQ > 200 milliseconds) (restrictive strategy). We analyzed the impact of the restrictive strategy on pacemaker implantation rate, duration of hospital stay, and 1-year mortality. RESULTS: Between January 2014 and December 2016, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs. 38.1%, p < .001) and length of hospital stay (intensive care unit 52 ± 55 vs. 60 ± 52 hours, p < .001; general ward 10.6 ± 5.7 vs. 11.5 ± 5.7 days, p = .001). One-year all-cause mortality was not significantly different between groups (14.1% vs. 11.7%, log-rank p = .28). However, sudden death was more frequent in the restrictive group (3.4% vs. 1.3%, log-rank p = .049). CONCLUSIONS: As compared to a liberal indication for PPI, a restrictive indication reduced PPI rate and length of hospital stay without significantly affecting all-cause mortality. The observed increase in the risk of sudden death with the restrictive PPI indication deserves further investigation.

3D mapping for the identification of the fossa ovalis in left atrial ablation procedures: a pilot study of a first step towards an electroanatomic-guided transseptal puncture.

AIMS: Transseptal puncture (TP) for left atrial (LA) catheter ablation procedures is routinely performed under fluoroscopic guidance. To decrease radiation exposure and increase safety alternative techniques are desirable. The aim of this study was to assess whether right atrial (RA) electroanatomic 3D mapping can reliably identify the fossa ovalis (FO) in preparation of TP. METHODS AND RESULTS: Between May 2019 and August 2019, electroanatomic RA mapping was performed before TP in 61 patients with paroxysmal or persistent atrial fibrillation. Three electroanatomic methods for FO identification, mapping catheter-induced FO protrusion, electroanatomic-guided analysis, and voltage mapping, were evaluated and compared with transoesophageal echocardiography (TOE). Mapping catheter-induced FO protrusion was feasible in 60 patients (98%) with a mean displacement of 6.8 ± 2.5 mm, confirmed by TOE, and proofed to be the most valuable and easiest marker for FO identification. Electroanatomic-guided analysis localized the FO midpoint consistently in the lower half (43 ± 7%) and posterior (18.2 ± 4.4 mm) to a line between coronary sinus and vena cava superior. Analysis of RA voltage maps during sinus rhythm (n = 40, low-voltage cut-off value 1.0 and 1.5 mV) allowed secure FO recognition in 33% and 18%, only. A step-by-step approach, combining FO protrusion (first step) with anatomy criteria in case of protrusion failure (second step) would have allowed for the correct localization of a TP site within the FO in all patients. CONCLUSION: Right atrial electroanatomic 3D mapping prior to TP proofed to be a simple tool for FO identification and may potentially be of use in the safe and radiation-free performance of TP prior to LA ablation procedures.

Amplified sinus-P-wave reveals localization and extent of left atrial low-voltage substrate: implications for arrhythmia freedom following pulmonary vein isolation.

AIMS: Presence of arrhythmogenic left atrial (LA) low-voltage substrate (LVS) is associated with reduced arthythmia freedom rates following pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF). We hypothesized that LA-LVS modifies amplified sinus-P-wave (APW) characteristics, enabling identification of patients at risk for arrhythmia recurrences following PVI. METHODS AND RESULTS: Ninety-five patients with persistent AF underwent high-density (>1200 sites) voltage mapping in sinus rhythm. Left atrial low-voltage substrate (<0.5 and <1.0 mV) was quantified in a 10-segment LA model. Amplified sinus-P-wave-morphology and -duration were evaluated using digitized 12-lead electrocardiograms (40-80 mm/mV, 100-200 mm/s). 12-months arrhythmia freedom following circumferential PVI was assessed in 139 patients with persistent AF. Left atrial low-voltage substrate was most frequently (84%) found at the anteroseptal LA. Characteristic changes of APW were related to the localization and extent of LA-LVS. At an early stage, LA-LVS predominantly located to the LA-anteroseptum and was associated with APW-prolongation (≥150 ms). More extensive LA-LVS involved larger areas of LA-anteroseptum, leading to morphological changes of APW (biphasic positive-negative P-waves in inferior leads). Severe LA-LVS involved the LA-anteroseptum, roof and posterior LA, but spared the inferior LA, lateral LA, and LA appendage. In this advanced stage, widespread LVS at the posterior LA abolished the negative portion of P-wave in the inferior leads. The delayed activation of the lateral LA and LA appendage produced the late positive deflections in the anterolateral leads, resulting in the "late-terminal P"-pattern. Structured analysis of APW-duration and -morphology stratified patients to their individual extent of LA-LVS (Grade 1: mean LA-LVS 4.9 cm2 at <1.0 mV; Grade 2: 28.6 cm2; Grade 3: 42.3 cm2; P < 0.01). The diagnostic value of APW-duration for identification of LA-LVS was significantly superior to standard P-wave-amplification (c-statistic 0.945 vs. 0.647). Arrhythmia freedom following PVI differed significantly between APW-predicted grades of LA-LVS-severity [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.18-4.83; P = 0.015 for Grade 1 vs. Grade 2; HR 1.79, 95% CI 1.00-3.21, P = 0.049 for Grade 2 vs. Grade 3). Arrhythmia freedom 12 months after PVI was 77%, 53%, and 33% in Grades 1, 2 and 3, respectively. CONCLUSION: Localization and extent of LA-LVS modifies APW-morphology and -duration. Analysis of APW allows accurate prediction of LA-LVS and enables rapid and non-invasive estimation of arrhythmia freedom following PVI.

Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology. METHODS: We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events. RESULTS: A total of 762 patients underwent randomization (378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation). The mean duration of follow-up was 1.5 years. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%, respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24). CONCLUSIONS: In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety. (Funded by Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.).

Need for pacemaker implantation in patients with normal QRS duration immediately after transcatheter aortic valve implantation.

AIMS: We sought to assess the need for permanent pacemaker implantation (PPI) in patients with QRS <120 ms in electrocardiogram (ECG) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We retrospectively analysed 1139 consecutive patients who underwent transfemoral TAVI between 2008 and 2016, receiving different valve types. All patients were surveyed by continuous ECG monitoring for 48 h, 12-lead ECGs starting immediately after procedure, as well as 24-h Holter recording the day before discharge. Indication for PPI was at the discretion of the attending physician. Among 760 patients with QRS <120 ms prior to the TAVI procedure, 400 patients showed QRS <120 ms immediately after procedure, whereas 360 patients had QRS ≥120 ms. In the group with QRS <120 ms, PPI was performed in 34 patients [8.5%; 95% confidence interval (CI) 5.6-11.2%] during the first week. Eight of the PPIs in the group with QRS <120 ms (2%; CI 0.8-3.5%) fulfilled Class I indications for PPI after TAVI, whereas 26 PPIs had different indications [left bundle branch block, sick sinus, low-grade atrioventricular (AV) block]. Complete AV block developed in three patients of the group of QRS <120 ms (0.75%; CI 0.0-1.7%), which in all cases occurred after the 48 h-surveillance period. During 1-year follow-up, 11 PPIs were performed (2.8%; CI 1.2-4.5%), thereof three PPI for Class I indications including one complete AV block. CONCLUSION: In patients with QRS duration <120 ms immediately after TAVI, the risk for complete AV block was low during the first week after TAVI and 1-year follow-up.

Rapid improvement in left ventricular function after sinus rhythm restoration in patients with idiopathic cardiomyopathy and atrial fibrillation.

AIMS: Sinus rhythm restoration (SRR) in patients with atrial fibrillation (AF) and heart failure may improve systolic function and impact on consecutive clinical management, but time course and potential predictors of response to SRR are uncertain. METHODS AND RESULTS: We prospectively studied 50 consecutive patients who presented in heart failure with reduced ejection fraction (EF) and concomitant AF. After exclusion of valvular and coronary artery disease patients underwent electrical cardioversion. Serial echocardiography, cardiac magnetic resonance imaging (cMRI), and 24-h electrocardiograms were performed at baseline, and on Days 3 and 40 following SRR. Baseline left ventricular EF of the study population (76% male, age 69 ± 11 years) was 30 ± 7%. Sustained SRR (≥3 days) significantly improved EF (Day 3: 43 ± 7%, n = 46; Day 40: 53 ± 9%, n = 34; P < 0.001) as quantified by echocardiography. Comparable results were obtained using cMRI (baseline: 29 ± 8%; Day 3: 42 ± 9%). Three patients showed no response to SRR (EF improvement <15%). The percentage of patients meeting current criteria for implantable cardioverter-defibrillator (ICD) implantation for primary prevention dropped from 76% (n = 38) to 11% (n = 3) on Day 40 following SRR. No specific clinical or echocardiographic factor predicting improved EF after SRR could be identified. CONCLUSION: The majority of patients presenting with non-ischaemic, non-valvular heart failure with reduced EF and concomitant AF show a significant and rapid improvement in EF following SRR. An attempt at SRR and reassessment of the need for ICD implantation after 40 days may be warranted in all such patients.

Extent and spatial distribution of left atrial arrhythmogenic sites, late gadolinium enhancement at magnetic resonance imaging, and low-voltage areas in patients with persistent atrial fibrillation: comparison of imaging vs. electrical parameters of fibrosis and arrhythmogenesis.

AIMS: Atrial fibrosis contributes to arrhythmogenesis in atrial fibrillation and can be detected by MRI or electrophysiological mapping. The current study compares the spatial correlation between delayed enhancement (DE) areas to low-voltage areas (LVAs) and to arrhythmogenic areas with spatio-temporal dispersion (ST-Disp) or continuous activity (CA) in atrial fibrillation (AF). METHODS AND RESULTS: Sixteen patients with persistent AF (nine long-standing) underwent DE-magnetic resonance imaging (1.25 mm × 1.25 mm × 2.5 mm) prior to pulmonary vein isolation. Left atrial (LA) voltage mapping was acquired in AF and the regional activation patterns of 7680 AF wavelets were analysed. Sites with ST-Disp or CA were characterized (voltage, duration) and their spatial relationship to DE areas and LVAs <0.5 mV was assessed. Delayed enhancement areas and LVAs covered 55% and 24% (P < 0.01) of total LA surface, respectively. Delayed enhancement area was present at 61% of LVAs, whereas low voltage was present at 28% of DE areas. Most DE areas (72%) overlapped with atrial high-voltage areas (>0.5 mV). Spatio-temporal dispersion and CA more frequently co-localized with LVAs than with DE areas (78% vs. 63%, P = 0.02). Regional bipolar voltage of ST-Disp vs. CA was 0.64 ± 0.47 mV vs. 0.58 ± 0.51 mV. All 28 ST-Disp and 56 CA areas contained electrograms with prolonged duration (115 ± 14 ms) displaying low voltage (0.34 ± 0.11 mV). CONCLUSION: A small portion of DE areas and LVAs harbour the arrhythmogenic areas displaying ST-Disp or CA. Most arrhythmogenic activities co-localized with LVAs, while there was less co-localization with DE areas. There is an important mismatch between DE areas and LVAs which needs to be considered when used as target for catheter ablation.

Important reduction of the radiation dose for pulmonary vein isolation using a multimodal approach.

Aims: The number of pulmonary vein isolation (PVI) ablation procedures is steadily increasing worldwide resulting in a substantial radiation exposure to patients and operators. The aim of our study was to reduce radiation exposure during these procedures to a critical amount without compromising patient safety. Methods and results: First, we assessed radiation exposure for primary PVI procedures over time (2005-2015) at the University Heart Center Freiburg-Bad Krozingen. Second, we prospectively evaluated in 52 patients, the efficacy and safety of a novel radiation reduction program (particularly applying an enhanced fluoroscopy pulse dose-reduction and optimized 3D-mapping system use). In 2035 primary PVI procedures, radiation exposure, assessed as estimated effective dose (eED in mSv, dose area product * 0.002 * conversion factor for females), fluoroscopy-time, and procedure-time decreased significantly from 2005 to 2015 (e.g. eED decreased from 9.3 (interquartile range (IQR) 6.4-13.4) mSv to 0.9 (IQR 0.5-1.6) mSv, p for trend <0.001). Importantly, application of the enhanced radiation reduction program further reduced eED to 0.4 mSv (IQR 0.3-0.6, P < 0.001 vs. control), a value not significantly different from slow-pathway ablation procedures (P = 0.41). Multiple linear regression analysis identified the radiation reduction program as the only independent variable associated with a decrease in radiation exposure. Conclusion: Radiation exposure during PVI decreased over the last decade and can further be reduced significantly by the implementation of an enhanced radiation reduction program.

Correlation between atrial fibrillation driver locations and complex fractionated atrial electrograms in patients with persistent atrial fibrillation.

INTRODUCTION: The aim of this study was to evaluate a spatial correlation between active atrial fibrillation (AF) drivers measured by electrocardiographic imaging and complex fractionated atrial electrograms (CFAEs) in patients with persistent AF. METHODS: Sixteen patients with persistent AF were included. A biatrial geometry relative to an array of 252-body-surface-electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms were signal-processed (ECVUE™, CardioInsight Technologies Inc., Cleveland, OH, USA) to identify AF drivers. Before driver ablation, a biatrial mapping using the NavX system (St. Jude Medical, St. Paul, MN, USA) was performed to identify CFAEs. CFAE and driver regions were then quantified and compared. RESULTS: AF was terminated by driver ablation in 11/16 (70%) patients. The mean number of ablated driver regions was 4 ± 1 per patient. The most frequent driver locations were the inferior left atrium and coronary sinus, the right pulmonary veins, and the right atrium. In 49/63 (78%) of the driver locations, more than 75% of the driver site showed CFAEs. The mean ablated driver area was 58 ± 24 cm2 (19 ± 11% of total surface area). The mean CFAE area was 178 ± 59 cm2 (49 ± 16%). The percentage of non-ablated CFAE area was 76 ± 13% of total CFAEs. In 9/11 patients with AF termination, the termination site showed CFAEs. CONCLUSIONS: There is a significant overlap between AF driver regions identified by the ECVUE™ system and CFAE areas identified by the NavX system. AF driver regions are smaller and mostly embedded in larger CFAE areas. Selective ablation of drivers in CFAE areas seems sufficient to terminate persistent AF in the majority of patients.

Clinical Impact of the Microembolic Signal Burden During Catheter Ablation for Atrial Fibrillation: Just a Lot of Noise?

OBJECTIVES: Microembolic signal detection by transcranial Doppler ultrasonography may be considered a surrogate for cerebral events during invasive cardiac procedures. However, the impact of the microembolic signal count during pulmonary vein isolation on the clinical outcome is not well evaluated. We investigated the effect of the microembolic signal count on the occurrence of new silent cerebral embolism measured by diffusion-weighted imaging (DWI)-magnetic resonance imaging (MRI), changes in neuropsychological testing, and the occurrence of clinical events during long-term follow-up after pulmonary vein isolation. METHODS: Pulmonary vein isolation was performed in 41 patients. The total microembolic signal burden (classified into "solid," "gaseous," and "equivocal") and sustained thromboembolic showers of greater than 30 seconds were recorded. Diffusion-weighted imaging-MRI and neuropsychological testing were performed before and after pulmonary vein isolation to assess for silent cerebral embolism and neuropsychological sequelae. Long-term follow-up was performed by telephone to assess for stroke/transient ischemic attack. RESULTS: A total of 68,729 microembolic signals (14,893 solid, 11,909 gaseous, and 41,927 equivocal) with an average of 1676 signals per patient and 42 thromboembolic showers were recorded. No correlation between the microembolic signal/thromboembolic shower count and the occurrence of new DWI lesions or neuropsychological capability was found. After a mean follow-up ± SD of 49 ± 4 months, 1 patient had an overt transient ischemic event, which was not associated with a high microembolic signal count. CONCLUSIONS: In this multicenter study, we found no impact of the intraprocedural microembolic symbol/thromboembolic shower count on the occurrence of new DWI lesions, neuropsychological capability, or overt neurologic deficits after pulmonary vein isolation. Thus, not only the microembolic signal count but also procedural/individual factors may contribute to commensurable clinical damage, which may challenge this method as a valid biomarker during pulmonary vein isolation.