Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers. METHODS AND RESULTS: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Quantitative assessment the longitudinal changes of pulmonary vascular counts in chronic obstructive pulmonary disease.

BACKGROUND: Chest computed tomography (CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients. MATERIALS AND METHODS: A total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5 mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface. RESULTS: Ntotal/LSA and N<5 mm/LSA changed from 1.16 ± 0.27 to 0.87 ± 0.2 and from 1.02 ± 0.22 to 0.78 ± 0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39 ± 0.21 to 0.74 ± 0.17 and from 1.18 ± 0.19 to 0.67 ± 0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r = - 0.738, - 0.529) and N<5 mm /LSA (r = - 0.729, -- .497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5 mm/LSA (r = 0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5 mm/LSA was (- 0.032, - 0.023) and (- 0.027) in normal and SAD, respectively. CONCLUSIONS: Quantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.

Abnormal Pulmonary Venous Filling: An Adjunct Feature in the Computed Tomography Pulmonary Angiogram Assessment of Chronic Thromboembolic Pulmonary Hypertension.

Background Hypodense filling defects within the pulmonary veins on computed tomography described as pulmonary vein sign (PVS) have been noted in acute pulmonary embolism and shown to be associated with poor prognosis. We evaluated venous flow abnormalities in chronic thromboembolic pulmonary hypertension (CTEPH) to determine its usefulness in the computed tomography assessment of CTEPH. Methods and Results Blinded retrospective computed tomography analysis of 50 proximal CTEPH cases and 3 control groups-50 acute pulmonary embolism, 50 nonthromboembolic cohort, and 50 pulmonary arterial hypertension. Venous flow reduction was assessed by the following: (1) presence of a filling defect of at least 2 cm in a pulmonary vein draining into the left atrium, and (2) left atrium attenuation (>160 Hounsfield units). PVS was most prevalent in CTEPH. Compared with all controls, sensitivity and specificity of PVS for CTEPH is 78.0% and 85.3% (95% CI, 64.0-88.5 and 78.6-90.6, respectively) versus 34.0% and 70.7% (95% CI, 21.2-48.8 and 62.7-77.8) in acute pulmonary embolism, 8.0% and 62% (95% CI, 2.2-19.2 and 53.7-69.8) in nonthromboembolic and 2.0% and 60% (95% CI, 0.1-10.7 and 51.7-67.9) in pulmonary arterial hypertension. In CTEPH, lobar and segmental arterial occlusive disease was most commonly associated with corresponding absent venous flow. PVS detection was highly reproducible (Kappa=0.96, 95% CI, 0.90-1.01, P<0.001). Conclusions PVS is easy to detect with higher sensitivity and specificity in CTEPH compared with acute pulmonary embolism and is not a feature of pulmonary arterial hypertension. Asymmetric enhancement of pulmonary veins may serve as an additional parameter in the computed tomography assessment of CTEPH and can be used to differentiate CTEPH from pulmonary arterial hypertension.

Focal Pulsed Field Ablation for Pulmonary Vein Isolation and Linear Atrial Lesions: A Preclinical Assessment of Safety and Durability.

BACKGROUND: A novel ablation and mapping system can toggle between delivering biphasic pulsed field (PF) and radiofrequency energy from a 9-mm lattice-tip catheter. We assessed the preclinical feasibility and safety of (1) focal PF-based thoracic vein isolation and linear ablation, (2) combined PF and radiofrequency focal ablation, and (3) PF delivered directly atop the esophagus. METHODS: Two cohorts of 6 swine were treated with pulsed fields at low dose (PFLD) and high dose (PFHD) and followed for 4 and 2 weeks, respectively, to isolate 25 thoracic veins and create 5 right atrial (PFLD), 6 mitral (PFHD), and 6 roof lines (radiofrequency+PFHD). Baseline and follow-up voltage mapping, venous potentials, ostial diameters, and phrenic nerve viability were assessed. PFHD and radiofrequency lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviated esophagus. All tissues were submitted for histopathology. RESULTS: Hundred percent of thoracic veins (25 of 25) were successfully isolated with 12.4±3.6 applications/vein with mean PF times of <90 seconds/vein. Durable isolation improved from 61.5% PFLD to 100% with PFHD (P=0.04), and all linear lesions were successfully completed without incurring venous stenoses or phrenic injury. PFHD sections had higher transmurality rates than PFLD (98.3% versus 88.1%; P=0.03) despite greater mean thickness (2.5 versus 1.3 mm; P<0.001). PF lesions demonstrated homogenous fibrosis without epicardial fat, nerve, or vessel involvement. In comparison, radiofrequency+PFHD sections revealed similar transmurality but expectedly more necrosis, inflammation, and epicardial fat, nerve, and vessel involvement. Significant ablation-related esophageal necrosis, inflammation, and fibrosis were seen in all radiofrequency sections, as compared with no PF sections. CONCLUSIONS: The lattice-tip catheter can deliver focal PF to durably isolate veins and create linear lesions with excellent transmurality and without complications. The PF lesions did not damage the phrenic nerve, vessels, and the esophagus.

Echocardiographic assessment in patients with atrial fibrillation (AF) and normal systolic left ventricular function before and after catheter ablation: If AF begets AF, does pulmonary vein isolation terminate the vicious circle?

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) can be curative. There are conflicting data on whether AF associated atrial and ventricular structural remodeling reverses after ablation. The aim of this study was to evaluate the hemodynamic effect of AF ablation in patients with preserved left ventricular ejection fraction (LVEF). METHODS: Forty three AF patients were studied (aged 56 ± 11 years; 29 male, 23% persistent AF, LVEF ≥ 50%) in whom RFCA was performed. Echocardiographic evaluation of atrial and ventricular diameters, volumes and strain imaging by two-dimensional speckle tracking were performed before and at least 6 months after RFCA. Nine patients had AF during baseline examination. RESULTS: A significant decrease in the left (LA) and right (RA) atrial volume and an increase in the LA strain were observed 15 ± 7 months after RFCA. In the subgroup with baseline sinus rhythm, the increment in LA strain was only borderline significant. An increase in RA, right ventricular (RV) and Biatrial strain was noticed (p < 0.05). LVEF and global longitudinal strain of the left ventricle (LV), however, did not improve substantially. CONCLUSIONS: Radiofrequency catheter ablation of AF in patients with preserved LV systolic function results in significant improvement in RA and RV function with a substantial reduction in LA and RA size. No deleterious impact of AF ablation on LA function was revealed.

Pulmonary vein antral isolation causes depolarization of vein sleeves: Implications for the assessment of isolation.

PURPOSE: Pulmonary vein isolation (PVI) for atrial fibrillation has been shown to result in inexcitability of a large fraction of pulmonary veins (PVs), but the mechanism is unknown. We investigated the mechanism of PV inexcitability by assessing the effects of PVI on the electrophysiology of PV sleeves. METHODS: Patients undergoing first-time radiofrequency PVI were studied. Capture threshold, effective refractory period (ERP), and excitability were measured in PVs and the left atrial appendage (LAA) before and after ablation. Adenosine was used to assess both transient reconnection and transient venous re-excitability. RESULTS: We assessed 248 veins among 67 patients. Mean PV ERP (249.7 ± 54.0 ms) and capture threshold (1.4 ± 1.6 mA) increased to 300.5 ± 67.1 and 5.7 ± 5.6 mA, respectively (P < .0001 for both) in the 26.9% PVs that remained excitable, but no change was noted in either measure in the LAA. In 16.3% of the 73.1% inexcitable veins, transient PV re-excitability (as opposed to reconnection) was seen with adenosine administration. CONCLUSIONS: Antral PVI causes inexcitability in a majority of the PVs, which can transiently be restored in some with adenosine. Among PVs that remain excitable, ERP and capture threshold increase significantly. These data imply resting membrane potential depolarization of the of PV myocardial sleeves. As PV inexcitability hampers the assessment of entrance and exit block, demonstrating transient PV re-excitability during adenosine administration helps ensure true isolation.

Preclinical Evaluation of Pulsed Field Ablation: Electrophysiological and Histological Assessment of Thoracic Vein Isolation.

BACKGROUND: Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA's efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms. METHODS: A femoral venous approach was used to gain right and left atrial access under general anesthesia in healthy swine. Baseline potentials in right superior pulmonary and inferior common vein and in SVC were assessed. Bipolar PFA was performed with monophasic (PFAMono) and biphasic (PFABi) waveforms in 7 and 7 swine sequentially and irrigated radiofrequency ablation in 3 swine. Vein potentials were then assessed acutely, and at ≈10 weeks; histology was obtained. RESULTS: All targeted veins (n=46) were successfully isolated on the first attempt in all cohorts. The PFABi waveform induced significantly less skeletal muscle engagement. Pulmonary vein isolation durability was assessed in 28 veins: including the SVC, durability was significantly higher in the PFABi group (18/18 PFABi, 10/18 PFAMono, 3/6 radiofrequency, P=0.002). Transmurality rates were similar across groups with evidence of nerve damage only with radiofrequency. Pulmonary vein narrowing was noted only in the radiofrequency cohort. The phrenic nerve was spared in all cohorts but at the expense of incomplete SVC encirclement with radiofrequency. CONCLUSIONS: In this chronic porcine study, PFA-based pulmonary vein and SVC isolation were safe and efficacious with demonstrable sparing of nerves and venous tissue. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.

A comprehensive multi-index cardiac magnetic resonance-guided assessment of atrial fibrillation substrate prior to ablation: Prediction of long-term outcomes.

INTRODUCTION: Multiple cardiac magnetic resonance (CMR)-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), left ventricular ejection fraction (LVEF), LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study. METHODS AND RESULTS: Eighty-nine patients (53% paroxysmal AF, 73% male) underwent comprehensive CMR study before first-time AF ablation (median follow-up 726 days [IQR: 418-1010 days]). The 3D late gadolinium-enhanced acquisition (1.5T, 1.3 × 1.3 × 2 mm) was quantified for fibrosis; LA volume and sphericity were assessed on manual segmentation at atrial diastole; LAEF and LVEF were quantified on multislice cine imaging. AF recurred in 43 patients (48%) overall (31 at 1 year). In the recurrence group, LA fibrosis was higher (42% vs 29%; hazard ratio [HR]: 1.032; P = .002), left atrial ejection fraction (LAEF) lower (25% vs 34%; HR: 0.063; P = .016) and LVEF lower (57% vs 63%; HR: 0.011; P = .008). LA volume (135 vs 124 mL) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (Model 1), additionally AF type (Model 2) and combined (Model 3). In Models 1 and 2, LA fibrosis, LAEF, and LVEF were independently associated with outcome, but only LA fibrosis was independent in Model 3 (HR: 1.021; P = .022). CONCLUSIONS: LAEF, LVEF, and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome.

Achieving durable mitral isthmus block: Challenges, pitfalls, and methods of assessment.

BACKGROUND AND OBJECTIVES: Macroreentrant atrial tachycardias often occur following atrial fibrillation ablation, most commonly due to nontransmural lesions in prior ablation lines. Perimitral atrial flutter is one such arrhythmia which requires ablation of the mitral isthmus. Our objectives were to review the literature regarding ablation of the mitral isthmus and to provide our approach for assessment of mitral isthmus block. METHODS: We review anatomical considerations, ablation strategies, and assessment of conduction block across the mitral isthmus, which is subject to several pitfalls. Activation sequence and spatial differential pacing techniques are discussed for assessment of both endocardial and epicardial bidirectional mitral isthmus block. RESULTS: Traditional methods for verifying mitral isthmus block include spatial differential pacing, activation mapping, and identification of double potentials. Up to 70% of cases require additional ablation in the coronary sinus (CS) to achieve transmural block. Interpretation of transmural block is subject to six pitfalls involving pacing output, differentiation of endocardial left atrial recordings from epicardial CS recordings, identification of a slowly conducting gap in the line, and catheter positioning during spatial differential pacing. Interpretation of unipolar electrograms can identify nontransmural lesions. We employ a combined epicardial and endocardial assessment of mitral isthmus block, which involves using a CS catheter for epicardial recording and a duodecapolar Halo catheter positioned around the mitral annulus for endocardial recording. CONCLUSIONS: The assessment of transmural mitral isthmus block can be challenging. Placement of an endocardial mapping catheter around the mitral annulus can provide a precise assessment of conduction across the mitral isthmus.

Combined assessment of left atrial volume parameters for predicting recurrence of atrial fibrillation following pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

OBJECTIVES: Our aim was to test the hypothesis that comprehensive simplified left atrial (LA) assessment derived from routine echocardiography may be more useful than assessment of LA volume alone for predicting atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). METHODS: We studied 156 patients with paroxysmal AF (PAF) who had undergone PVI. Echocardiography was performed within two days before PVI. Maximum (Max-LAVi) and minimum LA volume index (Min-LAVi) were calculated with the biplane modified Simpson's method, and then normalized to the body surface area. On the basis of previous findings, the predefined cutoff value of Max-LAVi for AF recurrence was set at Max-LAVi ≥ 34 mL/m2 . ΔLA volume index (ΔLAVi) was also calculated as Max-LAVi minus Min-LAVi. The follow-up period after PVI was 24 months. RESULTS: AF recurrence was observed in 35 patients. Multivariate logistic regression analysis showed that ΔLAVi (odds ratio [OR]: 1.131; 95% confidence interval [CI]: 1.057-1.221; P < 0.001) was an independent predictor of AF recurrence. Sequential logistic regression models for predicting AF recurrence revealed that a model based on clinical variables including age, gender and AF duration (χ2  = 1.65) was improved by the addition of Max-LAVi ≥ 34 mL/m2 (χ2  = 13.8; P < 0.001), and further improved by the addition of ΔLAVi (χ2  = 18.2; P = 0.036). Of note is that only 1.02 ± 0.10 minutes per patient was needed to obtain a comprehensive LA assessment that included Max-LAVi, Min-LAVi, and ΔLAVi. CONCLUSION: This easy-to-use comprehensive simplified LA approach from routine echocardiography may well have clinical implications for better management of PAF patients.

New tailored approach using a revised assessment of fragmented potentials for persistent atrial fibrillation: Early area defragmentation by modified CFAE module.

INTRODUCTION: Pulmonary vein isolation (PVI) is widely performed for atrial fibrillation (AFib). However, it is insufficient to maintain sinus rhythm (SR) in persistent and long persistent atrial fibrillation (Per-AFib). Ablation of complex fractionated atrial electrograms (CFAEs) is currently classified as class IIb, However, the concept of length of potential was different between the current CFAE module of CARTO system and the definition of CFAE potential. The current CFAE module was configured in the shortest complex interval (SCI) mode, in which the meaning of length of potential was the interval of each component of fragmented potentials. That was a part of the potential. On the other hand, the meaning of the definition of CFAE potential was the length of fragmented potential itself. The purpose of this study was to essentially evaluate fragmented potentials by revisiting in interval confidence level (ICL) mode and express them on the map and prospectively investigate the efficacy and prognosis of a new tailored approach for defragmentation, which is called early area defragmentation (EADF). METHODS AND RESULTS: We acquired atrial potentials by modified CFAE module in ICL mode (K-CFAE potential) and visualized the distribution of K-CFAE potential (K-CFAE map). We performed PVI, and we ablated the fragmented areas based on the K-CFAE map. We enrolled 77 patients in this study (control group: 84 patients). After 24-month follow-up, 75.3% were able to maintain SR. CONCLUSIONS: K-CFAE mapping faithfully represented the distribution of fragmented areas. PVI, together with our new tailored approach, EADF, was successful in treating Per-AFib.

Comparison of a high throughput day case atrial fibrillation ablation service in a local hospital with standard regional tertiary cardiac centre care.

AIMS: We investigated safety and efficacy of a high throughput atrial fibrillation (AF) ablation service within a local non-cardiac centre compared with matched patients at the regional tertiary cardiac centre. METHODS AND RESULTS: Patients were consented in clinic and pre-assessed by clerical staff. Locally, other than physicians, staff had no experience of ablation and were trained with simulations. Pulmonary vein isolation (PVI) was performed with conscious sedation, on uninterrupted anticoagulation for at least 4 weeks. No transoesophageal echocardiogram (TOE) was performed. A 28 mm Arctic Front Advance Cryoballoon was used. A 20 mm Achieve wire demonstrated PVI on a portable laptop-based EP recording system. Phrenic nerve function was monitored during right PVI. Finally, a transthoracic echocardiogram excluded a pericardial effusion. A Femostop was applied. Two hundred and seventy-six patients were matched. Average age was 61 ± 0.7 years, 39% female. CHA2DS2 VASc score varied from 0 to 7. Procedure time was significantly shorter at the local hospital (63.5 ± 1.1 vs. 101.7 ± 2.9 min, P < 0.0001). Fluoroscopy time (5.5 ± 0.2 vs. 12.6 ± 0.6 min, P < 0.0001) and fluoroscopy dose were lower (17.2 ± 2.1 vs. 97.6 ± 14.6 mGy, P < 0.0001). Successful PVI was achieved in all. The complication rate was low (5.4% vs. 6.3%, P = not significant). Four (1.4%) patients were not day case discharges. At 3 month follow-up, 54.3% had complete resolution, and 26.1% had improvement of symptoms. A total of 16.6% patients requested repeat procedures for ongoing symptoms. CONCLUSION: In experienced hands, cryoballoon for paroxysmal AF is delivered safely and effectively in a local centre. Outcomes remain excellent. These short, day case procedures allow utilization of non-cardiac centres. The service provides a model to meet increasing demands.

Pulmonary Arterial Hemodynamic Assessment by a Novel Index in Systemic Sclerosis Patients: Pulmonary Pulse Transit Time.

OBJECTIVES: Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension. METHODS: Twenty-five SSc patients as a study group and 25 age- and sex-matched healthy volunteers for the control group were recruited to the study. Right ventricle function parameters, such as tricuspid annular plane systolic excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right ventricular dimensions, right ventricle fractional area changes, and myocardial perfusion index (MPI) were measured and calculated. Pulmonary pulse transit time was defined as the time interval between the R-wave peak in the ECG and the corresponding peak late systolic pulmonary vein flow velocity. RESULTS: Right ventricle myocardial performance index (RVMPI) and eSPAP were significantly higher in the SSc group than the controls (p = 0.032, p = 0.012, respectively). Pulmonary pulse transit time and TAPSE was shorter in the patients with SSc (p = 0.006, p = 0.015, respectively). In correlation analysis, pPTT was inversely correlated with RVMPI (r = - 0.435, p = 0.003), eSPAP (r = - 0.434, p = 0.003), and disease duration (r = - 0.595, p = 0.003). Conversely, it positively correlated with TAPSE (r = 0.345, p = 0.022). CONCLUSION: pPTT was found to be shorter in SSc patients. pPTT might serve as a surrogate marker of pulmonary hemodynamics in patients with SSc, even prior to the development of pulmonary hypertension.

Cost effectiveness of focal impulse and rotor modulation guided ablation added to pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Although ablation with focal impulse and rotor modulation (FIRM), as an adjunct to pulmonary vein isolation (PVI), has been shown to decrease atrial fibrillation (AF) recurrence, cost-effectiveness has not been assessed. OBJECTIVE: We aimed to evaluate the cost effectiveness of FIRM-guided ablation when added to PVI in a mixed AF population. METHODS AND RESULTS: We used a Markov model to estimate the costs, quality-adjusted survival, and cost effectiveness of adding FIRM ablation to PVI. AF recurrence rates were based on 3-year data from the CONFIRM trial. Model inputs for event probabilities and utilities were obtained from literature review. Costs were based on Medicare reimbursement, wholesale acquisition costs, and literature review. Three-year total costs FIRM+PVI versus PVI alone were $27,686 versus $26,924. QALYs were 2.338 versus 2.316, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $34,452 per QALY gained. Most of the cost (65-81%) was related to the index ablation procedure. Lower AF recurrence generated cost offsets of $4,266, primarily due to a reduced need for medications and repeat ablation. Probabilistic sensitivity analysis demonstrated ICER below $100,000/QALY in 74% of simulations. CONCLUSION: Based on data from the CONFIRM study, the addition of FIRM to PVI does have the potential to be cost-effective due to higher quality-adjusted life years and lower follow-up costs. Value is sensitive to the incremental reduction in AF recurrence, and FIRM may have the greatest economic value in patients with greater AF symptom severity. Results from ongoing randomized trials will provide further clarity.

Ablation of paroxysmal atrial fibrillation using a second-generation cryoballoon catheter or contact-force sensing radiofrequency ablation catheter: A comparison of costs and long-term clinical outcomes.

INTRODUCTION: Although noninferiority of cryoballoon ablation (CBA) and radiofrequency catheter ablation for antral pulmonary vein isolation (APVI) has been reported in patients with paroxysmal atrial fibrillation (PAF), it is not clear whether contact force sensing (CF-RFA) and CBA with the second-generation catheter have similar procedural costs and long-term outcomes. The objective of this study is to compare the long-term efficacy and cost implications of CBA and CF-RFA in patients with PAF. METHODS AND RESULTS: A first APVI was performed in 146 consecutive patients (age: 63 ± 10 years, men: 95 [65%], left atrial diameter: 42 ± 6 mm) with PAF using CBA (71) or CF-RFA (75). Clinical outcomes and procedural costs were compared. The mean procedure time was significantly shorter with CBA than with CF-RFA (98 ± 39 vs. 158 ± 47 minutes, P < 0.0001). Despite a higher equipment cost in the CBA than the CF-RFA group, the total procedure cost was similar between the two groups (P = 0.26), primarily driven by a shorter procedure duration that resulted in a lower anesthesia cost. At 25 ± 5 months after a single ablation procedure, 51 patients (72%) in the CBA, and 55 patients (73%) in the CF-RFA groups remained free from atrial arrhythmias without antiarrhythmic drug therapy (P = 0.84). CONCLUSIONS: The procedure duration was approximately 60 minutes shorter with CBA than CF-RFA. The procedural costs were similar with both approaches. At 2 years after a single procedure, CBA and CF-RFA have similar single-procedure efficacies of 72-73%.

Pulmonary vein isolation with concomitant renal artery denervation is associated with reduction in both arterial blood pressure and atrial fibrillation burden: Data from implantable cardiac monitor.

BACKGROUND: Renal artery denervation (RDN) has provided incremental atrial fibrillation (AF) suppression after pulmonary vein isolation (PVI) in patients with AF in the setting of drug-resistant hypertension. OBJECTIVE: To assess the relationship between changes of mean blood pressure (BP) and AF recurrences/AF burden after PVI combined with RDN. METHODS: All patients from two randomized studies with symptomatic paroxysmal AF and/or persistent AF and resistant hypertension who underwent PVI-only (n=37) or PVI with RDN (n=39), and implantable cardiac monitor (ICM) implantation were eligible for this study. Mixed-effects linear models were used to investigate the effect of RDN on mean BP and mean AF burden and associations between the two during the 12-month follow-up. RESULTS: Concomitant RDN was associated with a significant reduction in both mean AF burden (2.43 [95% CI: 1.76-3.09] % vs 6.95 [95% CI: 5.44-8.45] %) and mean BP (104 [95% CI: 103-106] mm Hg vs 112 [95% CI: 110-113] mm Hg). Decrease in mean BP was positively correlated with decline in mean AF burden: reduction of 5-10 mm Hg was accompanied by a 7.0% decreased mean AF burden, with greater reduction (up to 20 mm Hg) associated with on average 17.7% lower mean AF burden. CONCLUSIONS: Renal artery denervation when added to PVI decreases AF recurrences, AF burden, and mean BP. Reduction in mean BP is associated with both AF burden and recurrences. Further large-scale studies are needed to define the mechanistic pathway(s) of the antiarrhythmic effects of RDN.

Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study.

INTRODUCTION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. METHODS AND RESULTS: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P < 0.001) doses. MBP fell further at 24 mg (ΔMBP: 27 ± 12 mmHg) and 18 mg (26 ± 13 mmHg) doses compared to 12 mg (22 ± 10 mmHg vs., P < 0.001). A significant reduction in AVB in patients >110 kg (65% vs. 91% in 70-110 kg group, P < 0.001) in response to adenosine was seen. CONCLUSION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI.

Spatial Relationships of Complex Fractionated Atrial Electrograms and Continuous Electrical Activity to Focal Electrical Sources: Implications for Substrate Ablation in Human Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate the spatial relationships of focal electrical sources (FSs) to complex fractionated atrial electrograms (CFAE) and continuous electrical activity (CEA). BACKGROUND: Fractionated atrial electrograms have been associated with atrial fibrillation (AF) drivers in computational studies and represent ablation targets in the management of persistent AF. METHODS: We included a subset of 66 patients (age: 63 [56, 67] years, 69% persistent AF) with electroanatomic data from the SELECT AF (Selective complex fractionated atrial electrograms targeting for atrial fibrillation) randomized control trial that compared the efficacy of CFAE with CEA ablation in AF patients undergoing pulmonary vein antral ablation. Focal sources were identified based on bipolar electrogram periodicity and QS unipolar electrogram morphology. RESULTS: A total of 77 FSs (median: 1 [1st quartile, 3rd quartile: 1, 2] per patient) were identified most commonly in the pulmonary vein antrum and left atrial appendage. The proportions of FSs inside CFAE and CEA regions were similar (13% vs. 1.3%, respectively; p = 0.13). Focal sources were more likely to be on the border zone of CFAEs than in CEAs (49% vs. 7.8%, respectively; p = 0.012). Following ablation, 53% of patients had ≥1 unablated extrapulmonary vein FS. The median number of unablated FS was higher in patients with AF recurrence post ablation than in patients without (median: 1 [0, 1] vs. 0 [0, 1], respectively; p = 0.026). CONCLUSIONS: One-half of the FSs detected during AF localized to the border of CFAE areas, whereas most of the FSs were found outside CEA areas. CFAE or CEA ablation leaves a number of FS unablated, which is associated with AF recurrence. These findings suggest that many CFAEs may arise from passive wave propagation, remote from FS, which may limit their therapeutic efficacy in AF substrate modification.

MRI Assessment of Ablation-Induced Scarring in Atrial Fibrillation: Analysis from the DECAAF Study.

BACKGROUND: There is limited knowledge on the extent and location of scarring that results from catheter ablation and its role in suppressing atrial fibrillation (AF). We examined the effect of atrial fibrosis and ablation-induced scarring on catheter ablation outcomes in AF. METHODS: We conducted a prospective multicenter study that enrolled 329 AF patients presenting for catheter ablation. Delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium was obtained preablation. Scarring was evaluated in 177 patients with a DE-MRI scan obtained 90 days postablation. We evaluated residual fibrosis, defined as preablation atrial fibrosis not covered by ablation scar. The primary outcome was freedom from recurrent atrial arrhythmia. RESULTS: In the analysis cohort of 177 patients, preablation fibrosis was 18.7 ± 8.7% of the atrial wall. Ablation aimed at pulmonary vein (PV) isolation was performed in 163 patients (92.1%). Ablation-induced scar averaged 10.6 ± 4.4% of the atrial wall. Scarring completely encircled all 4 PVs only in 12 patients (7.3%). Residual fibrosis was calculated at 15.8 ± 8.0%. At 325 days follow-up, 35% of patients experienced recurrent arrhythmia. Multivariable Cox proportional hazards models demonstrated that baseline atrial fibrosis (HR and 95% CIs) (1.09 [1.06-1.12], P < 0.001) and residual fibrosis (1.09 [1.05-1.13], P < 0.001) were associated with atrial arrhythmia recurrence, while PV encirclement and overall scar were not. CONCLUSIONS: Catheter ablation of AF targeting PVs rarely achieves permanent encircling scar in the intended areas. Overall atrial fibrosis present at baseline and residual fibrosis uncovered by ablation scar are associated with recurrent arrhythmia.

Assessment of atrial synchrony in paroxysmal atrial fibrillation and impact of pulmonary vein isolation for atrial dyssynchrony and global strain by three-dimensional strain echocardiography.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for ischemic stroke and congestive heart failure. AF may cause left atrial (LA) dyssynchrony as well as electrical and mechanical remodeling. The aim of this study was to investigate LA dyssynchrony in patients with paroxysmal AF (PAF) and its recovery after pulmonary vein isolation (PVI), using a three-dimensional strain method. METHODS: Thirty patients with PAF who underwent PVI were enrolled. Three-dimensional echocardiography was performed before and 3 months after PVI. Twenty subjects in whom AF had never been detected served as controls. LA dyssynchrony was quantified by the standard deviation of time to peak strain (TP-SD) from end-diastole by area tracking. Serial changes in TP-SD, LA volume, and global strain in three-dimensional echocardiography were investigated. RESULTS: In the PAF group, TP-SD was significantly higher (9.19 ± 4.98% vs 4.80 ± 2.30% in controls, P < .02) and global strain significantly lower (48.2 ± 20.2% vs 84.4 ± 32.9% in controls, P = .0003) than in the control group. TP-SD, global strain, and LA volume all improved significantly from before to after PVI (TP-SD, from 9.19 ± 4.98% to 6.31 ± 2.94%, P = .005; global strain, from 48.2 ± 20.2% to 58.1 ± 21.2%, P = .018; LA volume index, 29.5 ± 10.6 to 25.8 ± 7.1 mL/m(2), P = .04). Despite the improvement after PVI, TP-SD was still significantly higher and global strain lower than in controls. CONCLUSIONS: In patients with PAF, impaired LA function was documented by three-dimensional echocardiography. Despite early LA structural reverse remodeling, LA dyssynchrony was still observed 3 months after PVI. These results may affect medical therapy after successful PVI.