Determination of single cryoablation outcome within 30 to 60 seconds of freezing based on ice impedance.

BACKGROUND: A direct indicator of effective pulmonary vein isolation (PVI) based on early ice formation is presently lacking. OBJECTIVE: The initial impedance rise within 30 to 60 seconds (sec) of single cryoablation relating to ice on the distal surface of the cryoballoon could; predict effective PVI with early termination, the need for prolonging the cryoablation, or failure to achieve effective ablation. METHODS: Impedance measurements were taken between two ring electrodes, at the anterior balloon surface and at the shaft behind the balloon. Ice covering the anterior ring leads to impedance rise. Single cryoablation (eight animals, 37 veins) was applied for 90 to 180 sec. Cryoapplication was terminated if the impedance reached ≥500 Ω. Impedance levels at ≤60 sec of cryoablation were divided into three groups based on the characteristics of the impedance rise. PVI was confirmed acutely and at 45 ± 9 days recovery by electrophysiology mapping and histopathology. RESULTS: At 60 sec of freezing, an impedance rise of 34.1 ± 15.2 Ω (13-50 Ω) and slope of the impedance rise (measured during 15-30 sec of cryoapplication) less than 1 Ω/sec resulted in failed PVI. An impedance rise of 104.4 ± 31.5 Ω (76-159 Ω) and slope of 2 Ω/sec resulted in 100% PVIs. An impedance rise of 130.9 ± 137.8 Ω (40-590 Ω) and slope of 10 Ω/sec resulted in 100% PVIs with early termination at 90 sec. CONCLUSION: The efficacy of single cryoablation can be defined within 30 to 60 sec based on ice impedance. Three unique impedance profiles described in this investigation are associated with the uniformity and thickness of the ice buildup on the anterior surface of the balloon. One cryoablation with an adequate impedance rise is needed for successful outcomes.

Real-time magnetic resonance imaging-guided cryoablation of the pulmonary veins with acute freeze-zone and chronic lesion assessment.

AIMS: The goals of this study were to develop a method that combines cryoablation with real-time magnetic resonance imaging (MRI) guidance for pulmonary vein isolation (PVI) and to further quantify the lesion formation by imaging both acute and chronic cryolesions. METHODS AND RESULTS: Investigational MRI-compatible cryoablation devices were created by modifying cryoballoons and cryocatheters. These devices were used in canines (n = 8) and a complete series of lesions (PVI: n = 5, superior vena cava: n = 4, focal: n = 13) were made under real-time MRI guidance. Late gadolinium enhancement (LGE) magnetic resonance imaging was acquired at acute and chronic time points. Late gadolinium enhancement magnetic resonance imagings show a significant amount of acute tissue injury immediately following cryoablation which subsides over time. In the pulmonary veins, scar covered 100% of the perimeter of the ostium of the veins acutely, which subsided to 95.6 ± 4.3% after 3 months. Focal point lesions showed significantly larger acute enhancement volumes compared to the volumes estimated from gross pathology measurements (0.4392 ± 0.28 cm3 vs. 0.1657 ± 0.08 cm3, P = 0.0043). Additionally, our results with focal point ablations indicate that freeze-zone formation reached a maximum area after 120 s. CONCLUSION: This study reports on the development of an MRI-based cryoablation system and shows that with acute cryolesions there is a large area of reversible injury. Real-time MRI provides the ability to visualize the freeze-zone formation during the freeze cycle and for focal lesions reaches a maximum after 120 s suggesting that for maximizing lesion size 120 s might be the lower limit for dosing duration.

Towards a tailored cryo-pulmonary vein isolation. Lessons learned from second-generation cryoballoon ablation.

Second-generation cryoballoon ablation has emerged as an effective and practical approach for the treatment of atrial fibrillation. It gained the overall interest of the electrophysiology community due to its excellent success rates, and reproducible clinical outcomes comparable to the point-by-point radiofrequency technique. This technology offers several advantages including a fast learning curve and shorter procedure times making this device widely adopted in many EP-laboratories as an alternative strategy to conventional point-by-point radiofrequency ablation. As compared to its predecessor, the improved technical performances of the second-generation cryoballoon translated into favorable clinical outcomes, which are maintained in long-term follow-up. However, the ideal cryo-application duration and the adequate number of freeze-thaw cycles are not well established and predictors of durable electrical isolation are poorly known. This review provides some practical advices for a successful ablation using the second-generation cryoballoon.

Characteristics of Ice Impedance Recorded From a Ring Electrode Placed at the Anterior Surface of the Cryoballoon: Novel Approach to Define Ice Formation and Pulmonary Vein Isolation.

BACKGROUND: The success of cryoablation of the pulmonary vein isolation (PVI) is dependent on transmural and circumferential ice formation. We hypothesize that rising impedance recorded from a ring electrode placed 2 mm from the cryoballoon signifies ice formation covering the balloon surface and indicates ice expansion. The impedance level enables titration of the cryoapplication time to avoid extracardiac damage while ensuring PVI. METHODS AND RESULTS: In 12 canines, a total of 57 pulmonary veins were targeted for isolation. Two cryoapplications were delivered per vein with a minimum of 90 and maximum of 180-second duration. Cryoapplication was terminated on reaching a 500 Ω change from baseline. Animals recovered 38±6 days post-procedure, and veins were assessed electrically for isolation. Heart tissue was histologically analyzed. Extracardiac structures were examined for damage. PVI was achieved in 100% of the veins if the impedance reached 500 Ω in <90 seconds with freeze time of 90 seconds. When 500 Ω was reached >90 to 180 seconds (142.60±29.3 seconds), 90% PVI was achieved. When the final impedance was between 200 and 500 Ω with 180 seconds of freeze time, PVI was achieved in 86.8%. For impedance of <200 Ω, PVI was achieved in 14%. No extracardiac damage was recorded. CONCLUSIONS: Impedance rise of 500 Ω at <90 seconds with freeze time of 90 seconds resulted in 100% PVI. Impedance measurements from the nose of the balloon is a direct measure of ice formation on the balloon. It provides real-time feedback on the quality of the ablation and defines the cryoapplication termination time based on ice formation, limiting ice expansion to extracardiac tissues.

Dosing of the second-generation cryoballoon using acute time-to-pulmonary vein isolation as an indicator of durable ablation in a canine model.

BACKGROUND: Rigid time-based dosing protocol(s) currently used in the clinic for cryoballoon ablation of atrial fibrillation may be inadequate to guide the circumferential and transmural cryothermal energy transfer across the pulmonary vein (PV) and may result in injury to collateral tissues or electrical gaps between the PV and left atrium (LA). OBJECTIVE: A physiologic endpoint (e.g., acute time-to-PV isolation a.k.a. time-to-effect; TTE) may be effective in the determination of a transmural lesion formation and may allow for individualized ablation dosing across each PV. METHODS: Thirty PVs from 15 dogs were randomized into five dosing protocols, including (1) TTE + 60 s, (2) TTE + 90 s, (3) TTE + 120 s, (4) TTE + 150 s, and (5) 2 × 180 s. Ablations were conducted with a 23-mm second-generation cryoballoon, and TTE was assessed during a freeze by pacing from an inner balloon-lumen circular diagnostic catheter to a quadripolar diagnostic catheter in the coronary sinus. After ablation, animals were survived for 30 to 34 days, and repeat electrophysiology assessment of PV isolation was conducted after which animals were euthanized for gross anatomy and histological examination. RESULTS: At study termination, efficacy endpoint evaluations were based on maintenance of PV electrical isolation, gross anatomy assessment of PV lesions, and histological examination of PVs. Five efficacy endpoint failures were noted, including the following: 1 PV in the TTE + 90 sec group; 2 PVs in the TTE + 120 sec group; 1 PV in the TTE + 150 s group; and 1 PV in the 2 × 180 s group. Regarding safety, one phrenic nerve injury was observed in the 2 × 180 s cohort. No other complications were observed. CONCLUSIONS: In a canine model, effective PV isolation could be found even in the shortest duration dosing cohort (TTE + 60 s). One complication (phrenic nerve injury) was observed in the longest duration dosing group (2 × 180 s). Further studies will be required to correlate these results to a 28-mm cryoballoon (more commonly used in the cryoablation of a human LA); however, to date, this is the first reporting of a successful cryoablation using TTE + 60 s dosing (approximately 90 s total duration of freezing).

Novel dyeless and fluoro-less approach to cryoballoon pulmonary vein occlusion assessment.

BACKGROUND: Pulmonary vein (PV) occlusion is essential for PV isolation (PVI) using the cryoballoon. Currently occlusion is arbitrarily determined using fluoroscopy and contrast media. This study aimed to create an objective measure without utilizing excessive fluoroscopy and using no contrast media. OBJECTIVE: To ensure PV occlusion without fluoroscopy and contrast dye. METHODS: In 4 in vivo hearts 113 PV occlusions were tested with a 50% cold dye saline mix at 4°C. Occlusions were rated Good, Fair, and Poor by dye dissipation seen via fluoroscopy and correlated to temperature profiles recorded concurrently. Using these temperature profiles and no dye, cryoablations were placed in 12 additional hearts (56 unique veins, 126 occlusions). Two 180-second cryoablation applications were placed per vein with occlusion testing in between. PVI was defined by electrophysiology mapping, gross pathology, and histology after ≥4 weeks recovery. RESULTS: Dye results were as follows: With Good, Fair, and Poor the maximal postinjection PV temperature dropped (ΔT) by 6.2 ± 4.2°C, 5.1 ± 3.7°C, and 2.4 ± 2.0°C. At 5 seconds post nadir temperature, injection temperature recovered 18% ± 14%, 36% ± 23%, and 50% ± 33%. Console thaw time to 0°C was 11.5 ± 4.8 seconds, 8.5 ± 2.1 seconds, and 4.3 ± 1.3 seconds. Success rate for PVI was 100%, 97%, and 0%. With no dye: ΔT: 7.7 ± 4.4°C, 5.8 ± 5.0°C, and 3.4 ± 2.3°C; % recovery at 5 seconds: 15% ± 12%, 31% ± 23%, 45% ± 30%; thaw time to 0°C: 11.9 ± 4.8 seconds, 10.5 ± 5.2 seconds, 6.0 ± 2.8 seconds; success rate: 97%, 91%, and 10%. CONCLUSION: PV occlusion profile determination using 4°C cold saline injection is an effective approach to define the occlusion grade. Quality occlusions correlate strongly with PVI success.

Real-Time MRI-Guided Cardiac Cryo-Ablation: A Feasibility Study.

INTRODUCTION: MRI-based ablation provides an attractive capability of seeing ablation-related tissue changes in real time. Here we describe a real-time MRI-based cardiac cryo-ablation system. METHODS: Studies were performed in canine model (n = 4) using MR-compatible cryo-ablation devices built for animal use: focal cryo-catheter with 8 mm tip and 28 mm diameter cryo-balloon. The main steps of MRI-guided cardiac cryo-ablation procedure (real-time navigation, confirmation of tip-tissue contact, confirmation of vessel occlusion, real-time monitoring of a freeze zone formation, and intra-procedural assessment of lesions) were validated in a 3 Tesla clinical MRI scanner. RESULTS: The MRI compatible cryo-devices were advanced to the right atrium (RA) and right ventricle (RV) and their position was confirmed by real-time MRI. Specifically, contact between catheter tip and myocardium and occlusion of superior vena cava (SVC) by the balloon was visually validated. Focal cryo-lesions were created in the RV septum. Circumferential ablation of SVC-RA junction with no gaps was achieved using the cryo-balloon. Real-time visualization of freeze zone formation was achieved in all studies when lesions were successfully created. The ablations and presence of collateral damage were confirmed by T1-weighted and late gadolinium enhancement MRI and gross pathological examination. CONCLUSION: This study confirms the feasibility of a MRI-based cryo-ablation system in performing cardiac ablation procedures. The system allows real-time catheter navigation, confirmation of catheter tip-tissue contact, validation of vessel occlusion by cryo-balloon, real-time monitoring of a freeze zone formation, and intra-procedural assessment of ablations including collateral damage.

Histopathology of cryoballoon ablation-induced phrenic nerve injury.

INTRODUCTION: Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. METHODS AND RESULTS: A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. CONCLUSION: Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage.

Improved in vivo performance of second-generation cryoballoon for pulmonary vein isolation.

INTRODUCTION: A novel cryoballoon with improved refrigerant distribution promises better pulmonary vein (PV) isolation success rate without sacrificing the technology's safety profile. This study aimed to compare the Arctic Front® (AF) balloon to the new Arctic Front Advance™ (AFA). METHODS AND RESULTS: Twenty pulmonary PVs from 10 healthy dogs weighing 29.8 ± 1.1 kg were assigned to ablation with AF and AFA, using a 23 mm or 28 mm balloon. A single 4-minute ablation was performed in each vessel, with no phrenic nerve monitoring. The Achieve™ mapping catheter was used to confirm acute isolation. Thirty days post-treatment the ablation sites were assessed for electrical PV isolation and ablation completeness via gross and histological examination. The phrenic nerve, PVs, lungs, esophagus, kidneys, and brain were collected for evaluation of potential damage. A preprocedural and prenecropsy CT were performed to assess incidence of PV stenosis. All 10 PVs were fully isolated with AFA; 6 of 10 PVs were fully isolated with AF. In all cases, lesion gaps with AF are believed to stem from inadequate cooling of the most distal balloon segment that was in contact with the unablated PV tissue. No untoward findings were detected on gross examination of the heart, esophagus, kidneys, brain, or PVs. One phrenic nerve had cross-sectional ablation associated with an AFA 23 mm balloon. Superficial regions of subpleural lung fibrosis were noted adjacent to 7 PVs. CONCLUSIONS: PV isolation and lesion completeness were improved with Arctic Front Advance, while no unexpected findings were found related to safety.

Pulmonary vein isolation using a second-generation cryoballoon catheter: a randomized comparison of ablation duration and method of deflation.

INTRODUCTION: Optimal cryoballoon ablation parameters for pulmonary vein (PV) isolation remain to be defined. We conducted a randomized preclinical trial to compare 2- versus 4-minute ablation lesions and assess the safety of active (forced) cryoballoon deflation. METHODS AND RESULTS: Thirty-two dogs underwent PV isolation with a second-generation 23 mm cryoballoon catheter. The left superior (LSPV) and inferior (LIPV) PVs were randomized in a factorial design to (1) a single 2- versus 4-minute cryoapplication, and (2) passive versus active cryoballoon deflation. Animals were survived for 30 days, after which histopathologic analysis was performed. Acute PV isolation was attained in 89.8% of PVs after a single application (93.8% LSPV, 85.2% LIPV; P = 0.2823). Mean time to PV isolation was 29.5 ± 18.5 seconds. Although 4-minute lesions were associated with a thicker neointima than 2-minute lesions (223.8 µm versus 135.6 µm; P = 0.007), no differences were observed in procedural characteristics (freezing temperature, rewarming time), rates of acute PV isolation, or the achievement of complete circumferentially transmural lesions at 30 days (78.7% overall; 86.2% for 2 minutes vs 70.0% for 4 minutes; P = 0.285). Active deflation was associated with faster balloon rewarming but not with significant differences in mean or maximum neointimal thickness. CONCLUSION: A single application with the second-generation cryoballoon catheter results in a high rate of PV isolation. The degree of vascular injury was not increased by active balloon deflation and no differences in acute efficacy or mature transmural circumferential lesions were observed with 2- versus 4-minute applications.

Electrical impedance tomography's correlation to lung volume is not influenced by anthropometric parameters.

STUDY OBJECTIVES: Electrical impedance tomography (EIT) is able to reflect physiological parameters such as real-time changes in global and regional lung volume. EIT can aid in the assessment of lung recruitment, and its use has been validated in preliminary studies monitoring mechanical ventilation at the bedside. ICU patients vary widely in their body habitus, and obesity is becoming more prevalent. Our primary research purpose was to establish whether anthropometric parameters influence EIT's reliability. Our secondary question was whether body position alters its correlation to spirometric measurements. SUBJECTS: 22 healthy adult volunteers (12 male, 10 female) with broadly variable anthropometric parameters. INTERVENTIONS: Simultaneous measurements of changes in lung volume using EIT imaging and a pneumotachograph were obtained with two breathing patterns (quiet and deep breathing) and in four body positions (standing, sitting, semi-reclining and supine). MEASUREMENTS AND RESULTS: Correlation between measurements of changes in lung volume using EIT imaging and a pneumotachograph was excellent. Variations attributable to anthropometric measurements accounted for at most a 1.3% difference. CONCLUSIONS: Anthropometric variability and body position do not adversely influence the EIT estimation of changes in lung volume. These data suggest EIT could be used to monitor critically ill mechanically ventilated adults with variable body habitus regardless of position.

A parametric model of the relationship between EIT and total lung volume.

Spirometry and electrical impedance tomography (EIT) data from 26 healthy subjects (14 males, 12 females) were used to develop a model linking contrast variations in EIT difference images to lung volume changes. Eight recordings, each 64 s long, were made for each subject in four postures (standing, sitting, reclining at 45 degrees, supine) and two breathing modes (quiet tidal and deep breathing). Age, gender and five anthropometric variables were recorded. The database was divided into four subsets. The first subset, data from 22 subjects (12 males, 10 females) recorded in deep breathing mode, was used to create the model. Validation was done with the other subsets: data recorded during quiet tidal breathing in the same 22 subjects, and data recorded in both breathing modes for the other four subjects. A quadratic equation in DeltaV(P) (lung volume changes recorded by the spirometer) provided a very good fit to total contrast changes in the EIT images. The model coefficients were found to depend on posture, gender, thoracic circumference and scapular skin fold. To validate the model, the quadratic equation was inverted to estimate lung volume changes from the EIT images. The estimated changes were then compared to the measured volume changes. Validations with each data subset yielded mean standard errors ranging from 9.3% to 12.4%. The proposed model is a first step in enabling inter individual comparisons of EIT images since: (1) it provides a framework for incorporating the effects of anthropometric variables, gender and posture, and (2) it references the images to a physical quantity (volume) verifiable by spirometry.