Same-day discharge after cryoballoon ablation of atrial fibrillation: A multicenter experience.

BACKGROUND: It is common practice to observe patients during an overnight stay (ONS) following a catheter ablation procedure for the treatment of atrial fibrillation (AF). OBJECTIVES: To investigate the safety and economic impact of a same-day discharge (SDD) protocol after cryoballoon ablation for treatment of AF in high-volume, geographically diverse US hospitals. METHODS: We retrospectively reviewed 2374 consecutive patients (1119 SDD and 1180 ONS) who underwent cryoballoon ablation for AF at three US centers. Baseline characteristics, acute procedure-related complications, and longer-term evaluations of safety were recorded during routine clinical follow-up. The mean cost of an ONS was used in a one-way sensitivity analysis to evaluate yearly cost savings as a function of the percentage of SDD cases per year. RESULTS: The SDD and ONS cohorts were predominately male (69% vs. 67%; p = .3), but SDD patients were younger (64 ± 11 vs. 66 ± 10; p < .0001) with lower body mass index (30 ± 6 vs. 31 ± 61; p < .0001) and CHA2 DS2 -VASc scores (1.4 ± 1.0 vs. 2.2 ± 1.4; p < .0002). There was no difference between SDD and ONS in the 30-day total complication rate (n = 15 [1.26%] versus n = 24 [2.03%]; p = .136, respectively). The most common complication was hematoma in both the SDD (n = 8; 0.67%) and ONS (n = 11; 0.93%) cohorts. Sensitivity analysis demonstrated that when 50% of every 100 patients treated were discharged the same day, hospital cost savings ranged from $45 825 to $83 813 per year across US hospitals. CONCLUSIONS: SDD following cryoballoon ablation for AF appears to be safe and is associated with cost savings across different US hospitals.

Cryoballoon ablation dosing: From the bench to the bedside and back.

To date, multiple modes of research have been leveraged to study the optimal cryoballoon ablation parameters to safely, effectively, and efficiently isolate the pulmonary veins for the treatment of atrial fibrillation. Basic scientific investigation, preclinical studies, clinical observations, trials, and, more recently, computational modeling have helped to generate and test new hypotheses for the advancement of cryoballoon treatment in patients with atrial fibrillation. In this review, we examine the data and evidence that have contributed to the development of patient-tailored dosing strategies that are currently used for pulmonary vein isolation by using the Arctic Front series of cryoballoon ablation catheters.

Cryoballoon-to-Pulmonary Vein Occlusion Assessment via Capnography Technique: Where Does Occlusion Testing by End-Tidal CO2 Measurement "Fit" as a Predictor of Long-Term Efficacy?

INTRODUCTION: Parameters used to gauge the effectiveness of a cryoballoon lesion have been described that monitor the ablation at the time of balloon-to-pulmonary vein (PV) occlusion, during the cryoablation freeze, and at the thaw phase of the cryoablation. This study examines the balloon-to-PV occlusion step and monitors the completeness of occlusion using capnography to measure end-tidal CO2 (ETCO2). Specifically, the main objective was to determine if ETCO2 measurements can be used to quantify the amount of balloon-to-PV occlusion and to determine if acute ETCO2 parameters could predict long-term freedom from atrial fibrillation (AF). METHODS AND RESULTS: In a prospective study, 30 subjects were cryoballoon ablated for drug refractory symptomatic paroxysmal AF by pulmonary vein isolation method. During the balloon-to-PV occlusion and throughout the cryoablation, ETCO2 measurements were recorded. The subjects were followed for a 12-month period to monitor their freedom from AF. Five subjects had a recurrence of AF outside of a 90-day blanking period but before the 12-month endpoint. Between the 25 subjects that maintained normal sinus rhythm (NSR) and the 5 subjects that had recurrent AF (rAF), there were no statistical differences in procedural parameters, including: the number of cryoablations per PV, duration of each cryoablation, balloon nadir temperature, or balloon thaw time. Additionally, there were no statistical differences in baseline ETCO2 and in nadir ETCO2 between the two cohorts; however, when examining Δ ETCO2, the subjects in the NSR cohort had a significantly larger change compared to the rAF cohort (P<0.001). The largest change in ETCO2 during balloon-to-PV occlusion was observed during the cryoballoon ablation of the superior PVs; however, Δ ETCO2 did not solely predict long-term freedom from AF for the individual subject. CONCLUSION: Δ ETCO2 did tend to be larger in the NSR cohort compared to the rAF cohort; however, ETCO2 monitoring was more responsive in the superior PVs and less useful in the inferior PVs. Moreover, ETCO2 monitoring could not be used as a sole indicator of long-term efficacy. Suggesting that monitoring balloon-to-PV occlusion is a necessary first in cryoballoon ablation, but other parameters must be incorporated and observed as surrogates of a circumferential and transmural lesion formation with long-term durability.

Verification of a novel atrial fibrillation cryoablation dosing algorithm guided by time-to-pulmonary vein isolation: Results from the Cryo-DOSING Study (Cryoballoon-ablation DOSING Based on the Assessment of Time-to-Effect and Pulmonary Vein Isolation Guidance).

BACKGROUND: There are no recommendations on the optimal dosing for cryoablation of atrial fibrillation (Cryo-AF). OBJECTIVE: The purpose of this study was to develop and prospectively test a Cryo-AF dosing protocol guided exclusively by time-to-pulmonary vein (PV) isolation (TT-PVI) in patients undergoing a first-time Cryo-AF. METHODS: In this multicenter study, we examined the acute/long-term safety/efficacy of Cryo-AF using the proposed dosing algorithm (Cryo-AFDosing; n = 355) against a conventional, nonstandardized approach (Cryo-AFConventional; n = 400) in a nonrandomized fashion. RESULTS: Acute PV isolation was achieved in 98.9% of patients in Cryo-AFDosing (TT-PVI = 48 ± 16 seconds) vs 97.2% in Cryo-AFConventional (P = .18). Cryo-AFDosing was associated with shorter (149 ± 34 seconds vs 226 ± 46 seconds; P <.001) and fewer (1.7 ± 0.8 vs 2.9 ± 0.8; P <.001) cryoapplications, reduced overall ablation (16 ± 5 minutes vs 40 ± 14 minutes; P <.001), fluoroscopy time (13 ± 6 minutes vs 29 ± 13 minutes; P <.001), left atrial dwell time (51 ± 14 minutes vs 118 ± 25 minutes; P <.001), and total procedure time (84 ± 23 minutes vs 145 ± 49 minutes; P <.001) but similar nadir balloon temperature (-47°C ± 8°C vs -48°C ± 6°C; P = .41) and total thaw time (43 ± 27 seconds vs 45 ± 19 seconds; P = .09) as compared to Cryo-AFConventional. Adverse events (2.0% vs 2.7%; P = .48), including persistent phrenic nerve palsy (0.6% vs 1.2%; P = .33) and 12-month freedom from all atrial arrhythmias (82.5% vs 78.3%; P = .14), were similar between Cryo-AFDosing and Cryo-AFConventional. However, Cryo-AFDosing was specifically associated with fewer atypical atrial flutters/tachycardias during long-term follow-up (8.5% vs 13.5%; P = .02) as well as fewer late PV reconnections at redo procedures (5.0% vs 18.5%; P <.001). CONCLUSION: A novel Cryo-AF dosing algorithm guided by TT-PVI can help individualize the ablation strategy and yield improved procedural endpoints and efficiency as compared to a conventional, nonstandardized approach.

First description of a double-wall balloon breach during cryoballoon ablation for atrial fibrillation.

BALLOON BREACH DURING CRYOABLATION: To date, this is the first published report of a double-wall breach while using the cryoballoon ablation catheter during the treatment of a patient with atrial fibrillation; however, there have been previous balloon breaches in both the second and third-generation cryoballoon ablation catheter usage. In this report, we describe the case of a double-wall balloon breach and the intraoperative care that was necessary to stabilize the patient. Additionally, we review other known cases of double-wall balloon breaches, and we examine the safety systems of the cryoballoon catheter that mitigate some of the potential patient complications.

Catheter ablation using the third-generation cryoballoon provides an enhanced ability to assess time to pulmonary vein isolation facilitating the ablation strategy: Short- and long-term results of a multicenter study.

BACKGROUND: Limited data exist on cryoablation of atrial fibrillation (Cryo-AF) using the newly available third-generation (Arctic Front Advance-Short Tip [AFA-ST]) cryoballoon. OBJECTIVE: In this multicenter study, we evaluated the safety and efficacy of Cryo-AF using the AFA-ST vs the second-generation (Arctic Front Advance [AFA]) cryoballoon. METHODS: We examined the procedural safety and efficacy and the short- and long-term clinical outcomes associated with a first-time Cryo-AF performed in 355 consecutive patients (254/355 [72%] with paroxysmal AF), using either the AFA-ST (n = 102) or the AFA (n = 253) cryoballoon catheters. RESULTS: Acute isolation was achieved in 99.6% of all pulmonary veins (PVs) (AFA-ST: 100% vs AFA: 99.4%; P = .920). Time to pulmonary vein isolation was recorded in 89.2% of PVs using AFA-ST vs 60.2% using AFA (P < .001). PVs targeted using AFA-ST required fewer applications (1.6 ± 0.8 vs 1.7 ± 0.8; P = .023), whereas there were no differences in the balloon nadir temperature (AFA-ST: -47.0°C ± 7.3°C vs AFA: -47.5°C ± 7.8°C; P = .120) or thaw time (AFA-ST: 41 ± 24 seconds vs AFA: 44 ± 28 seconds; P = .056). However, AFA-ST was associated with shorter left atrial dwell time (43 ± 5 minutes vs 53 ± 16 minutes; P < .001) and procedure time (71 ± 11 minutes vs 89 ± 25 minutes; P < .001). Furthermore, Cryo-AF using AFA-ST was completed more frequently by "single-shot" PV ablation (27.4% vs 20.2%; P = .031). Persistent phrenic nerve palsy (AFA-ST: 0% vs AFA: 0.8%; P = .507) and procedure-related adverse events (AFA-ST: 1.0% vs AFA: 1.6%; P = .554) were similar, as was the freedom from recurrent atrial arrhythmias at 10 months of follow-up (AFA-ST: 81.8% vs AFA: 79.9%; P = .658). CONCLUSION: Cryo-AF using the AFA-ST cryoballoon offers an enhanced ability to assess time to pulmonary vein isolation, allowing for fewer cryoapplications and shorter left atrial dwell time and procedure time. Consequently, this allowed for procedural completion more frequently using a "single-shot" PV ablation with equivalent safety and efficacy.

Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial.

AIMS: The primary safety and efficacy endpoints of the randomized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current (RFC) catheter ablation in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF). The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses. Specifically, reinterventions, rehospitalizations, and quality-of-life were examined in this randomized trial of cryoballoon vs. RFC catheter ablation. METHODS AND RESULTS: Patients (374 subjects in the cryoballoon group and 376 subjects in the RFC group) were evaluated in the modified intention-to-treat cohort. After the index ablation, log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations (11.8% cryoballoon vs. 17.6% RFC; P = 0.03), direct-current cardioversions (3.2% cryoballoon vs. 6.4% RFC; P = 0.04), all-cause rehospitalizations (32.6% cryoballoon vs. 41.5% RFC; P = 0.01), and cardiovascular rehospitalizations (23.8% cryoballoon vs. 35.9% RFC; P < 0.01). There were no statistical differences between groups in the quality-of-life surveys (both mental and physical) as measured by the Short Form-12 health survey and the EuroQol five-dimension questionnaire. There was an improvement in both mental and physical quality-of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up. CONCLUSION: Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations, direct-current cardioversions, all-cause rehospitalizations, and cardiovascular rehospitalizations during follow-up. Both patient groups improved in quality-of-life scores after AF ablation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490814.

Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter.

The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) - the atrial septum's thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P <0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a "cryoballoon only" technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures.

Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids.

BACKGROUND: Low levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials. OBJECTIVE: We examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo. METHODS: Our novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C. RESULTS: Co-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05). CONCLUSIONS: HDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.

Quantification of the cryoablation zone demarcated by pre- and postprocedural electroanatomic mapping in patients with atrial fibrillation using the 28-mm second-generation cryoballoon.

BACKGROUND: There are 2 Food and Drug Administration-approved catheters (ThermoCool RF and Arctic Front Advance cryoballoon) for the treatment of drug refractory and symptomatic paroxysmal atrial fibrillation. Each tool is used to ablate the area surrounding the pulmonary veins (PVs). However, no study has described and quantified the ablated surface area after the application of cryoablation lesions with the second-generation cryoballoon. OBJECTIVE: The purpose of this study was to determine the area of ablation during cryoballoon PV isolation. METHODS: Preprocedural computed tomography angiography of the left atrium (LA) was conducted in 43 patients to accurately determine spatial chamber dimensions. Before and after the ablation procedure, a detailed 3-dimensional electroanatomic map of the LA was created and merged onto the computed tomography angiogram to improve the accuracy of the data recordings. RESULTS: The posterior LA wall had a mean surface area of 31.1 (±1.6 SEM) cm(2). Left- and right-sided antral PV surface areas of cryoballoon ablation were not statistically different (P = .935), which were 11.4 (±0.8 SEM) and 11.3 (±0.8 SEM) cm(2), respectively. In total, 27% of the posterior LA wall remained unablated, electrically functional, and homogeneous with regard to voltage conductivity. This ablation strategy resulted in 95.3% freedom from atrial fibrillation at 6 months. CONCLUSION: The area of the posterior LA wall ablation with the cryoballoon catheter is wide and antral, and the resulting posterior LA wall debulking could be a part of the cryoballoon efficacy beyond discrete PV isolation.

Acute procedural and cryoballoon characteristics from cryoablation of atrial fibrillation using the first- and second-generation cryoballoon: a retrospective comparative study with follow-up outcomes.

PURPOSE: There is limited data available on the safety and efficacy of the second-generation cryoballoon (CB-2) for cryoablation of atrial fibrillation (Cryo-AF). We evaluated the procedural, biophysical, and clinical outcomes of Cryo-AF in a large patient cohort using CB-2 as compared with the first-generation cryoballoon (CB-1). METHODS: Three-hundred and forty consecutive patients undergoing Cryo-AF with CB-1 (n = 140) and CB-2 (n = 200) were retrospectively evaluated. RESULTS: Paroxysmal AF was more prevalent in CB-1 (86%) versus CB-2 (72%) (p = 0.001). During Cryo-AF, the mean balloon temperature was lower with CB-2 at 30 s (8 versus -4°C; p < 0.001) and 60 s (-26 versus -32°C; p < 0.001) with equivalent nadir temperatures (both at -50°C; p = 0.542). With CB-2, time-to-nadir temperature was shorter (232 versus 209 s; p < 0.001) and thaw times were longer (47 versus 53 s; p < 0.001). Acute pulmonary vein (PV) isolation rate was higher with CB-2 (92 versus 98%; p = 0.036) despite reduced cryoablation time (61 versus 47 min; p < 0.001) and freeze area-under-the-curve (-155,044 versus -116,740 s°C; p < 0.001). With CB-2, procedure time (209 versus 154 min; p < 0.001) and fluoroscopy time (42 versus 27 min; p < 0.001) were shorter, with similar acute/long-term adverse events (AEs) and freedom from AF at 6, 9, and 12 months (89, 86, and 82%) during 16 ± 8 months of follow-up. However, CB-2 was associated with lower PV reconnection rates at redo ablation (30 versus 13%; p = 0.037). CONCLUSIONS: With CB-2, acute and long-term PV isolation rates were higher despite shorter ablations, faster balloon cooling, and longer thaw times, with similar AE rates and freedom from AF.

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

BACKGROUND: Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. METHODS: A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. RESULTS: In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). CONCLUSION: This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

Atrioesophageal fistula during cryoballoon ablation for atrial fibrillation.

To date, there is 1 case report publication of AE fistula during the employment of the first-generation cryoballoon (Gen-1). Recently the Arctic Front Advance system (second-generation cryoballoon) was introduced into the US and EU markets. For the purpose of peer education, we report a case of AE fistula that occurred during the utilization of the second-generation cryoballoon (Gen-2). Additionally, we review current best practices that may reduce the risk of AE fistula during any AF ablation procedure.

Using a cardiac anchor to refine myocardial infarction surgery in the rat.

Researchers have used the rat model of myocardial infarction for more than 20 y to successfully mimic the detrimental effects of coronary occlusion of the left anterior descending (LAD) coronary artery in humans. But researchers have published little about this surgery's intricacies or about the pathological progression of the disease after surgery. The authors describe a refined technique that uses a suture anchor at the apex of the heart, which allows easy and accurate placement of a ligature around the LAD. Furthermore, they detail the pathological timeline for the deposition of collagen in the injured left ventricle, a hallmark of myocardial infarction. Researchers can use this refined technique to easily create a rat myocardial infarction and use the pathophysiological markers described herein to follow disease progression.

Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice.

BACKGROUND: Cardiac-targeted expression of truncated K(v)4.2 subunit (K(v)4.2N) reduces transient outward current (I(to)) density, prolongs action potentials (APs), and enhances contractility in 3- to 4-week-old transgenic mice. By 13 to 15 weeks of age, these mice develop severely impaired cardiac function and signs of heart failure. In this study, we examined whether augmented contractility in K(v)4.2N mice results from elevations in intracellular calcium ([Ca2+]i) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of K(v)4.2N mice. METHODS AND RESULTS: At 3 to 4 weeks of age, L-type Ca2+ influx and peak [Ca2+]i were significantly elevated in K(v)4.2N myocytes compared with control because of AP prolongation. Cardiac calcineurin activity was also significantly elevated in K(v)4.2N mice by 5 weeks of age relative to controls and increased progressively as heart disease developed. This was associated with activation of protein kinase C (PKC)-alpha and PKC-theta but not PKC-epsilon, as well as increases in beta-myosin heavy chain (beta-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented increases in heart weight to body weight ratios, interstitial fibrosis, impaired contractility, PKC activation, and changes in the expression patterns of beta-MHC and SERCA2a. CONCLUSIONS: Our results demonstrate that AP prolongation caused by I(to) reduction results in enhanced Ca2+ cycling and hypercontractility in mice and suggests that elevations in [Ca2+]i via I(Ca,L) and activation of calcineurin play a central role in disease development after I(to) reduction using the K(v)4.2N construct.