Ultralow temperature cryoablation using near-critical nitrogen for cavotricuspid isthmus-ablation, first-in-human results.

INTRODUCTION: Cryoablation has evolved as a safe alternative to radiofrequency ablation in the treatment of several supraventricular arrhythmias and has potential advantages, yet is limited by the properties of the cryogen used. We investigated a novel ultralow temperature cryoablation (ULTC) system using nitrogen near its liquid-vapor critical point as a freezing source, achieving temperatures as low as -196 degrees Celsius in a long linear catheter with a continuous energy release. Initial safety, procedural and efficacy outcomes of ULTC are described in patients undergoing cavotricuspid isthmus (CTI) ablation. METHODS AND RESULTS: The Cryocure studies (NCT02355106, NCT02839304) are prospective, single-arm, multi-center, first-in-human clinical studies in 17 patients with atrial flutter (AFL) and 13 patients with atrial fibrillation (AF). A total of 30 patients, mean age 65 ± 8 years old and 67% male, were enrolled and underwent ablation of the CTI. Acute success, defined as the confirmation of stable bidirectional conduction block across the CTI, was achieved in all 30 patients. After 12 months of follow-up, 14 out of 17 AFL patients remained free from any AFL. One (3.3%) procedure-related but not device-related serious adverse event was reported, involving transient inferolateral ST-elevation associated with temporary AV conduction block. CONCLUSION: In this first-in-human clinical study the safety and performance results demonstrate the capabilities of ultralow temperature near-critical nitrogen as an effective energy source for CTI ablation. Ongoing, larger, studies should confirm our findings and evaluate the capabilities to create linear and focal transmural lesions in other arrhythmias.

Ultralow temperature cryoablation: Safety and efficacy of preclinical atrial and ventricular lesions.

BACKGROUND: Ultralow temperature cyroablation (ULTC) is designed to create focal, linear, and circumferential lesions. The aim of this study was to assess the safety, efficacy, and durability of atrial and ventricular ULTC lesions in preclinical large animal models. METHODS AND RESULTS: The ULTC system uses nitrogen near its liquid-vapor critical point to cool 11-cm ablation catheters. The catheter can be shaped to specific anatomies using pre-shaped stylets. ULTC was used in 11 swine and four sheep to create atrial (pulmonary vein isolation and linear ablation) and ventricular lesions. Acute and 90-day success were evaluated by intracardiac mapping and histologic examination. Cryoadherence was observed during all ULTC applications, ensuring catheter stability at target locations. Local electrograms were completely eliminated immediately after the first single-shot ULTC application in 49 of 53 (92.5%) atrial and in 31 of 32 (96.9%) ventricular applications. Lesion depth as measured on histology preparations was 1.96 ± 0.8 mm in atrial and 5.61 ± 2.2 mm in ventricular lesions. In all animals, voltage maps and histology demonstrated transmural and durable lesions without gaps, surrounded by intact collagen fibers without injury to surrounding tissues. Transient coronary spasm could be provoked with endocardial ULTC in the left ventricle in close proximity to a coronary artery. CONCLUSIONS: ULTC created effective and efficient atrial and ventricular lesions in vivo without procedural complications in two large animal models. ULTC lesions were transmural, contiguous, and durable over 3 months.

Compatibility assessment of a temperature-controlled radiofrequency catheter with a novel electroanatomical mapping system.

Background: The novel DiamondTemp ablation system (DTA) and EnSiteX mapping System (EAM) are both CE-Marked and FDA approved medical devices. The DTA has been validated by its manufacturer only in combination with previous version of EnSite System-EnSite Precision. The aim of this study was to evaluate compatibility of DTA with EnSite X with a previously developed protocol. Methods: Three configurations were tested: 3.1. Medtronic Generator connection Box (GCB) and AmpereConnect cable; 3.2. the Medtronic GCB-E and electrogram out cable from GCB to EAM; 3.3. Direct connection of DTA to EAM using intracardiac out cable with no GCB. Results: The previously developed universal method for compatibility assessment of ablation catheters and navigation systems was used with success for assessing DTA and EnSite X EAM compatibility, with reproducible results. Accuracy of DTA visualization with different setups was evaluated with a phantom model measuring distances between DTA and reference points. DTA is compatible with EnSiteX EAM with a safety and reliability profile guaranteed, if within the described specifications. In particular, careful setup is mandatory to achieve good clinical outcomes as only setup 3.2 is viable for both NavX and Voxel Mode and demonstrated satisfactory results and accuracy. Setup 3.3 showed a significant shift immediately after catheter insertion. Catheter position was away from baseline points and the dislocation increased during the radiofrequency delivery. Conclusions: Previously developed method for compatibility assessment of ablation catheters and navigation systems has been used for a new EAM. DTA is compatible with EnSiteX EAM with proper configuration.

Universal Method of Compatibility Assessment for Novel Ablation Technologies With Different 3D Navigation Systems.

Background: New technologies for ablation procedures are often produced by different companies with no cross-compatibility out of the box. This is not a negligible clinical problem since those separately developed devices are often used together. The aim of this study was to develop a bench-testing method to assess compatibility between the DiamondTemp ablation system (DTA) and the Rhythmia electroanatomic mapping system (EAM). Methods: Different setups were tested. DTA was connected to the Rhythmia EAM using the following configurations: 3.1. An Ensite EPT GenConnect box (GCB) and Rhythmia Maestro GCB (Maestro GCB, native Rhythmia setup); 3.2. The Medtronic GCB-E and Maestro GCB; 3.3. The Medtronic GCB-E out via the Medtronic GCB-E directly to the Rhythmia at box 1 (pin A61 to A64). Results: The DTA location was represented in real-time on the Rhythmia EAM. A proper tracking of the DTA was observed in all setups tested by visual comparison of physical catheter movements and its representation on EAM. In configuration 3.1, a significant shift was observed after the first radio frequency (RF) application; however, further applications caused no further shift. In setup 3.2, no significant shift was observed. The setup 3.3 showed a massive shift in the catheter position before ablation compared to baseline points acquired using the Orion catheter as a reference. Conclusions: A universal and reproducible solution for compatibility testing between the various mapping systems and the ablation catheters has been described. DTA has been demonstrated as compatible with Rhythmia EAM with satisfactory results if a specific setup is used.

Cortisol suppression after memory reactivation impairs later memory performance.

Experiencing stressful or traumatic events can result in disabling clinical symptoms of maladaptive emotional memory retrieval, which are only partly addressed by the currently proposed treatments. Cortisol modulation has been shown to affect emotional memory retrieval and potentially reconsolidation, offering an opportunity for developing more efficient treatments for disorders with an emotional memory component. Here, we investigated if cortisol suppression after reactivation of emotional memories weakens later memory thereof. Forty healthy young men were tested in a randomized, placebo controlled, double-blind, and between-subject design, assigned either to a cortisol suppression (metyrapone) group or a placebo group. Participants of both groups, were presented with two emotional stories at an encoding session (Day 1). One of the two stories was later reactivated and followed by metyrapone vs. placebo administration (Day 3). Memory for both stories was tested at a recognition memory session (Day 7). In the group undergoing cortisol suppression after memory reactivation memory performance was weaker compared to the placebo group, tested four days after reactivation. This study shows that cortisol suppression can weaken memory for past events, possibly by altering reconsolidation processes and thus exerting long-lasting weakening effects on the original memory.

Remote magnetic navigation for mapping and ablation of right and left ventricular outflow tract arrhythmias.

OBJECTIVE: The aim of this study was to assess the efficacy and potential complications of a remote-controlled magnetic navigation system (Niobe II, Stereotaxis) for mapping and ablation of right or left ventricular outflow tract ventricular tachycardia or premature ventricular contractions. METHODS: We studied 32 consecutive patients, mean age 43±11 years, 24 female. Mapping of the arrhythmia was performed using the CARTO RMT mapping system, remotely guided by the Niobe II. Radiofrequency ablation was performed at the site of earliest ventricular activation with pacemapping of at least 11/12 leads. Acute success was defined as suppression and non-inducibility of the arrhythmia after stimulation with isoprenaline. After a minimum 3-month follow-up, we assessed clinical success (absence of symptoms and suppression of the arrhythmia on Holter recording), defined as less than 50 premature ventricular contractions/24 hours. RESULTS: The origin of the arrhythmia was in the right ventricular outflow tract in 28 patients (88%), in the left in three, and in the epicardium in one. Acute success was achieved in 26 patients (81%). Two patients underwent a second successful procedure, in one of which an epicardial approach was necessary. The overall clinical success rate, after two repeat procedures, was 88%. No complications occurred. There were two recurrences during a mean follow-up of 307±204 days. CONCLUSION: The Niobe II remote control system for mapping and ablation of ventricular outflow tract arrhythmias is effective and safe, and provides precise mapping and a high success rate, with no complications.