Ultra-high-resolution assessment of lesion extension after cryoballoon ablation for pulmonary vein isolation.

Introduction: Unrecognized incomplete pulmonary vein (PV) isolation during the index procedure, can be a major cause of clinical recurrences of atrial fibrillation (AF) after cryoballoon (CB) ablation. We aimed to characterize the extension of the lesions produced by CB ablation and to assess the value of using an ultra-high resolution electroanatomic mapping (UHDM) system to detect incomplete CB lesions. Materials and methods: Twenty-nine consecutive patients from the CHARISMA registry undergoing AF ablation at four Italian centers were prospectively evaluated. The Rhythmia™ mapping system and the Orion™ (Boston Scientific) mapping catheter were used to systematically map the left atrium and PVs before and after cryoablation. Results: A total of 116 PVs were targeted and isolated. Quantitative assessment of the lesions revealed a significant reduction of the antral surface area of the PV, resulting in an ablated area of 5.7 ± 0.7 cm2 and 5.1 ± 0.8 cm2 for the left PV pair and right PV pair, respectively (p = 0.0068). The mean posterior wall (PW) area was 22.9 ± 2 cm2 and, following PV isolation, 44.8 ± 6% of the PW area was ablated. After CB ablation, complete isolation of each PV was documented by the POLARMap™ catheter in all patients. By contrast, confirmatory UHDM and the Lumipoint™ tool unveiled PV signals in 1 out of 114 of the PVs (0.9%). Over 30-day follow-up, no major procedure-related adverse events were reported. After a mean follow-up of 333 days, 89.7% of patients were free from arrhythmia recurrence. Conclusion: The lesion extension achieved by the new CB ablation system involved the PV antrum, with less than 50% of the PW remaining untouched. The new system, with short tip and circular mapping catheter, failed to achieve PV isolation in only 0.9% of all PVs treated. Clinical trial registration: [http://clinicaltrials.gov/], identifier [NCT03793998].

Novel cryoballoon ablation system for pulmonary vein isolation: multicenter assessment of efficacy and safety-ANTARCTICA study.

AIMS: Pulmonary vein isolation (PVI) either by balloon devices or radiofrequency forms the cornerstone of invasive atrial fibrillation (AF) treatment. Although equally effective cryoballoon (CB)-based PVI offers shorter procedure duration and a better safety profile. Beside the worldwide established Arctic Front Advance system, a novel CB device, POLARx, was recently introduced. This CB incorporates unique features, which may translate into improved efficacy and safety. However, multicentre assessment of periprocedural efficacy and safety is lacking up to date. METHODS AND RESULTS: A total of 317 patients with paroxysmal or persistent AF were included and underwent POLARx CB-based PVI in 6 centres from Germany and Italy. Acute efficacy and safety were assessed in this prospective multicenter observational study. In 317 patients [mean age: 64 ± 12 years, 209 of 317 (66%) paroxysmal AF], a total of 1256 pulmonary veins (PVs) were identified and 1252 (99,7%) PVs were successfully isolated utilizing mainly the short tip POLARx CB (82%). The mean minimal CB temperature was -57.9 ± 7°C. Real-time PVI was registered in 72% of PVs. The rate of serious adverse events was 6.0% which was significantly reduced after a learning curve of 25 cases (9.3% vs. 3.0%, P = 0.018). The rate of recurrence-free survival after mean follow-up of 226 ± 115 days including a 90-day blanking period was 86.1%. CONCLUSION: In this large multicentre assessment, the novel POLARx CB shows a promising efficacy and safety profile after a short learning curve.

Clinical and economic impact of multipoint left ventricular pacing: A comparative analysis from the Italian registry on multipoint pacing in cardiac resynchronization therapy (IRON-MPP).

INTRODUCTION: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs. METHODS: The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP-enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP-ON) or without (MPP-OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates. RESULTS: The study included 190 MPP-OFF and 128 MPP-ON patients with similar baseline characteristics. At 1 and 2 years, the MPP-ON group had lower rates of HFH vs MPP-OFF (1-year hazard ratio [HR]: 0.14, P = .0014; 2-year HR: 0.38, P = .009). The finding persisted in a subgroup of patients with consistent MPP activation through follow-up (1-year HR: 0.19; P = .0061; 2-year HR: 0.39, P = .022). Total HFH per-patient costs were lower in the MPP-ON vs the MPP-OFF group at 1 year (€101 ± 50 vs €698 ± 195, P < .001) and 2 years (€366 ± 149 vs €801 ± 203, P = .038). More MPP-ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P = .025) and clinical composite score (66.7% vs 47.5%, P = .01). CONCLUSIONS: In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow-up.

Long-term follow-up analysis of a highly characterized arrhythmogenic cardiomyopathy cohort with classical and non-classical phenotypes-a real-world assessment of a novel prediction model: does the subtype really matter.

AIMS: To provide long-term outcome data on arrhythmogenic cardiomyopathy (ACM) patients with non-classical forms [left dominant ACM (LD-ACM) and biventricular ACM (Bi-ACM)] and an external validation of a recently proposed algorithm for ventricular arrhythmia (VA) prediction in ACM patients. METHODS AND RESULTS: Demographic, clinical, and outcome data were retrieved from all ACM patients encountered at our institution. Patients were classified according to disease phenotype (R-ACM; Bi-ACM; LD-ACM). Overall and by phenotype long-term survival were calculated; the novel Cadrin-Tourigny et al. algorithm was used to calculate the a priori predicted VA risk, and it was compared with the observed outcome to test its reliability. One hundred and one patients were enrolled; three subgroups were defined (R-ACM, n = 68; Bi-ACM, n = 14; LD-ACM, n = 19). Over a median of 5.41 (2.59-8.37) years, the non-classical form cohort experienced higher rates of VAs than the classical form [5-year freedom from VAs: 0.58 (0.43-0.78) vs. 0.76 (0.66-0.89), P = 0.04]. The Cadrin-Tourigny et al. predictive model adequately described the overall cohort risk [mean observed-predicted risk difference (O-PRD): +6.7 (-4.3, +17.7) %, P = 0.19]; strafing by subgroup, excellent goodness-of-fit was demonstrated for the R-ACM subgroup (mean O-PRD, P = 0.99), while in the Bi-ACM and LD-ACM ones the real observed risk appeared to be underestimated [mean O-PRD: -20.0 (-1.1, -38.9) %, P < 0.0001; -22.6 (-7.8, -37.5) %, P < 0.0001, respectively]. CONCLUSION: Non-classical ACM forms appear more prone to VAs than classical forms. The novel prediction model effectively predicted arrhythmic risk in the classical R-ACM cohort, but seemed to underestimate it in non-classical forms.

Efficacy of cryoballoon ablation in patients with paroxysmal atrial fibrillation without time to pulmonary vein isolation assessment.

BACKGROUND: Real-time visualization of the electrical activity of the pulmonary veins (PV) is not always possible in the setting of atrial fibrillation (AF) cryoballoon ablation. We investigated the relation between the effective documentation of time to PV isolation and the clinical outcome in a cohort of patients with paroxysmal AF who underwent cryoballoon ablation. METHODS: One thousand forty two consecutive patients were enrolled. An inner lumen mapping catheter was typically used to visualize real-time electrical activity inside the PVs. RESULTS: Time to PV isolation was documented in all targeted PVs in 391 patients (Group 1), in 651 patients it was not possible to record PV potentials and assess time to PV isolation in at least one PV (Group 2). In Group 1 a longer procedure duration and ablation time were observed, while a longer fluoroscopy time was observed in Group 2. After a mean follow-up of 14 ±â€¯11 months, 209/1042 (20%) patients had an atrial arrhythmia recurrence (20.2% in Group 1, 19.9% in Group 2, p = 0.25). Complications occurred in 54/1042 (5.2%) patients without any difference among the two study groups. CONCLUSION: In our retrospective analysis, in about two thirds of patients undergoing cryoballoon ablation it was not possible to acutely assess time to PV isolation in all PVs. However, one-year freedom from clinically symptomatic atrial tachyarrhythmia was similar to that of patients in which time to PV isolation was documented in all targeted veins. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT01007474).

Impact of Female Sex on Clinical Outcomes in the FIRE AND ICE Trial of Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Data on predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation (AF) are limited. We sought to assess the association of baseline covariates with clinical outcomes in the 750 patients with drug-refractory paroxysmal AF enrolled in FIRE AND ICE. METHODS: In a 2-part analysis, univariate and multivariable Cox regression models were first used to identify baseline patient characteristics predictive of catheter ablation efficacy determined by the clinical end points of (1) atrial arrhythmia recurrence (primary efficacy failure), (2) cardiovascular rehospitalization, and (3) repeat ablation. Propensity score stratification methods were then used to account for differences in baseline characteristics between sexes. RESULTS: Female sex (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.08-1.73; P=0.010) and prior direct current cardioversion (HR, 1.40; 95% CI, 1.07-1.82; P=0.013) were independently associated with atrial arrhythmia recurrence. Female sex (HR, 1.36; 95% CI, 1.02-1.80; P=0.035) and hypertension (HR, 1.48; 95% CI, 1.09-2.00; P=0.013) independently predicted cardiovascular rehospitalization. A longer history of AF (HR, 1.03; 95% CI, 1.00-1.06; P=0.039) increased the rate of repeat ablation. Women continued to have higher rates of primary efficacy failure and cardiovascular rehospitalization after propensity score adjustment, with adjusted HRs of 1.51 (95% CI, 1.16-2.18; P<0.05) and 1.40 (95% CI, 1.15-2.17; P<0.05), respectively. CONCLUSIONS: After catheter ablation of paroxysmal AF, female sex was associated with an almost 40% increase in the risks of primary efficacy failure and cardiovascular rehospitalization. Primary efficacy failure was also adversely impacted by a history of direct current cardioversion, whereas hypertension had a negative impact on cardiovascular rehospitalization. History of AF was the only predictor of repeat ablation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01490814.

Prognostic Benefit of Cardiac Magnetic Resonance Over Transthoracic Echocardiography for the Assessment of Ischemic and Nonischemic Dilated Cardiomyopathy Patients Referred for the Evaluation of Primary Prevention Implantable Cardioverter-Defibrillator Therapy.

BACKGROUND: The aim of this study was to determine the prognostic benefit of cardiac magnetic resonance (CMR) over transthoracic echocardiography (TTE) in ischemic cardiomyopathy and nonischemic dilated cardiomyopathy patients evaluated for primary prevention implantable cardioverter-defibrillator therapy. METHODS AND RESULTS: We enrolled 409 consecutive ischemic and dilated cardiomyopathy patients (mean age: 64±12 years; 331 men). All patients underwent TTE and CMR, and left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricle ejection fraction (LVEF) were evaluated. In addition, late gadolinium enhancement was also assessed. All patients were followed up for major adverse cardiac events (MACE) defined as a composite end point of long runs of nonsustained ventricular tachycardia, sustained ventricular tachycardia, aborted sudden cardiac death, or sudden cardiac death. The median follow-up was 545 days. CMR showed higher left ventricle end-diastolic volume (mean difference: 43±22.5 mL), higher left ventricle end-systolic volume (mean difference: 34±20.5 mL), and lower LVEF (mean difference: -4.9±10%) as compared to TTE (P<0.01). MACE occurred in 103 (25%) patients. Patients experiencing MACE showed higher left ventricle end-diastolic volume, higher left ventricle end-systolic volume, and lower LVEF with both imaging modalities and higher late gadolinium enhancement per-patient prevalence as compared to patients without MACE. At multivariable analysis, CMR-LVEF ≤35% (hazard ratio=2.18 [1.3-3.8]) and the presence of late gadolinium enhancement (hazard ratio=2.2 [1.4-3.6]) were independently associated with MACE (P<0.01). A model based on CMR-LVEF ≤35% or CMR-LVEF ≤35% plus late gadolinium enhancement detection showed a higher performance in the prediction of MACE as compared to TTE-LVEF resulting in net reclassification improvement of 0.468 (95% confidence interval, 0.283-0.654; P<0.001) and 0.413 (95% confidence interval, 0.23-0.63; P<0.001), respectively. CONCLUSIONS: CMR provides additional prognostic stratification as compared to TTE, which may have direct impact on the indication of implantable cardioverter-defibrillator implantation.

Simultaneous assessment of contact pressure and local electrical coupling index using robotic navigation.

PURPOSE: Contact with cardiac tissue is a determinant of lesion efficacy during atrial fibrillation (AF) ablation. The Sensei®X Robotic Catheter System (Hansen Medical, CA) has been validated for contact force sensing. The electrical coupling index (ECI) from the EnSite Contact™ system (St. Jude Medical, MN) has been validated as an indicator of tissue contact. We aimed at analyzing ECI behavior during radiofrequency (RF) pulses maintaining a stable contact through the robotic navigation contact system. METHODS: In 15 patients (age, 59 ± 12) undergoing AF ablation, pulmonary vein (PV) isolation was guided by the Sensei®X System, employing the Contact™ catheter. RESULTS: During the procedure, we assessed ECI changes associated with adequate contact based on the IntelliSense® force-sensing technology (Hansen Medical, CA. Baseline contact (27 ± 8 g/cm(2)) ECI value was 99 ± 13, whereas ECI values in a noncontact site (0 g/cm(2)) and in a light contact site (1-10 g/cm(2)) were respectively 66 ± 12 and 77 ± 10 (p < 0.0001). Baseline contact ECI values were not different depending on AF presentation (paroxysmal AF, 98 ± 9; persistent AF, 100 ± 9) or on cardiac rhythm (sinus rhythm, 97 ± 7; AF,101 ± 10). In all PVs, ECI was significantly reduced during and after ablation (ECI during RF, 56 ± 15; ECI after RF, 72 ± 16; p < 0.001). A mean reduction of 32.2% during RF delivery and 25.4% immediately after RF discontinuation compared with baseline ECI was observed. CONCLUSIONS: Successful PV isolation is associated with a significant decrease in ECI of at least 20 %. This may be used as a surrogate marker of effective lesion in AF ablation.

[Catheter ablation of atrial fibrillation: Health Technology Assessment Report from the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)]. / Ablazione transcatetere della fibrillazione atriale. Health Technology Assessment Report dell'Associazione Italiana di Aritmologia e Cardiostimolazione (AIAC).

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and significantly impact patients' quality of life, morbidity and mortality. The number of affected patients is expected to increase as well as the costs associated with AF management, mainly driven by hospitalizations. Over the last decade, catheter ablation techniques targeting pulmonary vein isolation have demonstrated to be effective in treating AF and preventing AF recurrence. This Health Technology Assessment report of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) aims to define the current role of catheter ablation of AF in terms of effectiveness, efficiency and appropriateness. On the basis of an extensive review of the available literature, this report provides (i) an overview of the epidemiology, clinical impact and socio-economic burden of AF; (ii) an evaluation of therapeutic options other than catheter ablation of AF; and (iii) a detailed presentation of clinical outcomes and cost-benefit ratio associated with catheter ablation. The costs of catheter ablation of AF in Italy were obtained using a bottom-up analysis of a resource utilization survey of 52 hospitals that were considered a representative sample, including 4 Centers that contributed with additional unit cost information in a separate questionnaire. An analysis of budget impact was also performed to evaluate the impact of ablation on the management costs of AF. Results of this analysis show that (1) catheter ablation is effective, safe and superior to antiarrhythmic drug therapy in maintaining sinus rhythm; (2) the cost of an ablation procedure in Italy typically ranges from €8868 to €9455, though current reimbursement remains insufficient, covering only about 60% of the costs; (3) the costs of follow-up are modest (about 8% of total costs); (4) assuming an adjustment of reimbursement to the real cost of an ablation procedure and a 5-10% increase in the annual rate of ablation procedures, after approximately 5-6 years this would result in significant incremental savings for the Italian Healthcare System. In conclusion, catheter ablation of AF is a cost-effective procedure that is inadequately reimbursed in Italy. Insufficient reimbursement may serve as disincentive to perform AF ablation, thereby limiting patient access to this treatment. Considering the healthcare system perspective, higher initial costs for ablation procedures in the short term may be offset by cost savings mainly associated with decreased hospitalizations over time.

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration.

BACKGROUND: The autonomic nervous system (ANS) plays an important role in the genesis and maintenance of atrial fibrillation (AF), but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP) series during adrenergic activation induced by isoproterenol (a sympathomimetic drug) infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 +/- 6) underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii) sinus rhythm during isoproterenol (SRISO) administration; iii) atrial fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO) administration. The level of organization between two electrograms was assessed by the synchronization index (S), whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R). In addition, the level of predictability (LP) and regularity of LAP series were computed. RESULTS: LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (RSR = 0.75 +/- 0.07 RSRISO = 0.69 +/- 0.10, p < 0.0001; RAF = 0.31 +/- 0.08 RAFISO = 0.26 +/- 0.09, p < 0.0001; LPSR = 99.99 +/- 0.001 LPSRISO = 99.97 +/- 0.03, p < 0.0001; LPAF = 69.46 +/- 21.55 LPAFISO = 55 +/- 24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR (RSR = 0.49 +/- 0.08 RSRISO = 0.46 +/- 0.09 p < 0.0001) and in AF (RAF = 0.29 +/- 0.09 RAFISO = 0.28 +/- 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF.