Novel cryoballoon to isolate pulmonary veins in patients with paroxysmal atrial fibrillation: long-term outcomes in a multicentre clinical study.

BACKGROUND: Recently, a novel cryoballoon ablation catheter has demonstrated acute safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (PAF). However, there are limited studies demonstrating the long-term efficacy. The aim of this study was to evaluate the long-term safety and efficacy of this novel cryoballoon in treating PAF. METHODS: This was a non-randomized, prospective, multicentre study enrolling 58 consecutive patients. Cryoablation was delivered for 180 s if time to isolation was ≤ 60 s. Otherwise a 240-s cryoablation was performed. One centre performed pre- and post-ablation high-density mapping (n = 9) to characterize lesion formation. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. All patients were followed for 1 year. RESULTS: Acute PVI was achieved in 230 of 231 pulmonary veins (99.6%) with 5.3 ± 1.6 cryoablations per patient (1.3 ± 0.7 cryoablations per vein). Forty-three (77%) patients remained arrhythmia-free at 1-year follow-up. Four patients (6.9%) experienced phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post-index procedure. For patients who underwent high-density mapping, cryoablation was antral with 50% of the posterior wall ablated. CONCLUSIONS: Initial multicentre clinical experience with a novel cryoballoon has demonstrated safety and efficacy of PVI in patients with PAF. Ablation with this cryoballoon provides a wide, antral lesion set with significant debulking of the posterior wall of the left atrium.

Evaluation of lozenges containing egg yolk antibody against Porphyromonas gingivalis gingipains as an adjunct to conventional non-surgical therapy in periodontitis patients: A randomized controlled clinical trial.

BACKGROUND: In a previous pilot study, one-time application of anti-Porphyromonas gingivalis gingipain egg yolk immunoglobulin (IgY) into scaling and root planing (SRP)-treated periodontal pockets showed profound improvement of clinical and bacteriological parameters in patients with chronic periodontitis. The present study aims to evaluate the efficacy of daily use of lozenges fortified with the antibody as an adjunct to non-surgical therapy in patients with periodontitis. METHODS: Sixty-four patients with periodontitis were divided randomly into a test and a placebo group. The groups were treated by SRP followed by a daily use of lozenges containing either specific IgY against P. gingivalis gingipains (test) or a sham-immune IgY (placebo). Gingival bleeding index (GBI), probing pocket depth (PD) and quantitation of P. gingivalis in the gingival pockets were assessed at baseline and 8 weeks after the initiation of treatment and compared by using Wilcoxon signed rank test, Mann-Whitney U-test or t test. RESULTS: Both groups showed significant improvement of all parameters at 8 weeks post treatment (P < 0.001). There was a significant difference in reduction of GBI (P < 0.001) and P. gingivalis cell counts (P < 0.05) in the test group compared with the placebo group. The reduction of PD was greater in the test group compared with the placebo group although there was no statistically significant difference between the two groups. CONCLUSIONS: The adjunctive use of lozenges containing IgY antibody against gingipains from P. gingivalis resulted in clinical and microbiological benefits in the treatment for chronic periodontitis. Additional investigations are needed to examine if the IgY brings benefits to case patients who do not receive SRP.

Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound.

Stabilized microbubble ultrasound contrast agents (UCA) have potential to aid tissue ablation during ultrasound surgery by enhancing both cavitational and thermal damage mechanisms. Previously, we showed UCA infused at a rate of 1 microL/kg/min prior to ultrasound exposure could reduce the total energy required to produce tissue damage by up to two orders of magnitude. In this paper, we evaluate thresholds for macroscopic tissue damage with UCA infusion rates (IR) of 0.1, 0.3, 1, 3, and 10 microL/kg/min to determine IR potentially effective for ultrasound therapy. Canine kidneys were surgically externalized and insonified with single exposures of focused ultrasound. Incident exposures were 1.44 MHz tone bursts, either 250 ms in duration with intensity between 500 W/cm2 and 3200 W/cm2, or 100 micros to 1 s in duration with intensity equal to 3200 W/cm2. Probabilities of tissue damage occurrence were determined for each set of exposure conditions (intensity, duration, and IR). A threshold intensity and threshold duration, defined as the quantities for which tissue damage occurred with probability equal to 0.5, were estimated for each IR. Results show that, as IR increased from 0.1 to 10 microL/kg/min, the threshold intensity decreased by up to a factor of 3, and threshold duration decreased by up to a factor of 200. Microbubble introduction at IR up to 10 microL/kg/min thus may be effective in aiding ultrasound therapy.

Evaluation of ultrasound tissue damage based on changes in image echogenicity in canine kidney.

Sufficiently high intensity ultrasound can create hyperechoic regions in an ultrasound image due to local bubble generation. We explore the link between the temporal extent of these hyperechoic regions and tissue damage caused by ultrasound therapy. The decay rate of increased echogenicity from the focal zone in insonated live exteriorized canine kidney was quantified and correlated to the spatial extent of tissue damage. The decay half-time, t(half), defined as the time for echogenicity enhancement to decay by a factor of 2, was observed in all cases to be greater than 41 s in spatial zones in which extensive histological damage was observed. In cases in which the measured thalf was less than 11 s, the damage was limited to minor hemorrhage, or it was not detected. These t(half) discrimination boundaries of 41 and 11 s were not statistically different for cases in which contrast agent was used to enhance therapeutic efficiency. This was true even though contrast agent infusion significantly reduced the therapy pulse duration threshold for damage production.

Microbubble-enhanced cavitation for noninvasive ultrasound surgery.

Experiments were conducted to explore the potential of stabilized microbubbles for aiding tissue ablation during ultrasound therapy. Surgically exteriorized canine kidneys were irradiated in situ using single exposures of focused ultrasound. In each experiment, up to eight separate exposures were placed in the left kidney. The right kidney was then similarly exposed, but while an ultrasound contrast agent was continually infused. Kidneys were sectioned and examined for gross observable tissue damage. Tissue damage was produced more frequently, by lower intensity and shorter duration exposures, in kidneys irradiated with the contrast agent present. Using 250-ms exposures, the minimum intensity that produced damage was lower in kidneys with microbubbles than those without (controls) in 10 of 11 (91%) animals. In a separate study using approximately 3200 W/cm2 exposures, the minimum duration that produced damage was shorter after microbubbles were introduced in 11 of 12 (92%) animals. With microbubbles, gross observable tissue damage was produced with exposure intensity > or = approximately 800 W/cm2 and exposure duration > or = 10 micros. The overall intensity and duration tissue damage thresholds were reduced by approximately 2x and approximately 100x, respectively. Results indicate that acoustic cavitation is a primary damage mechanism. Lowering in vivo tissue damage thresholds with stabilized microbubbles acting as cavitation nuclei may make acoustic cavitation a more predictable, and thus practical, mechanism for noninvasive ultrasound surgery.

Controlled ultrasound tissue erosion.

The ability of ultrasound to produce highly controlled tissue erosion was investigated. This study is motivated by the need to develop a noninvasive procedure to perforate the neonatal atrial septum as the first step in treatment of hypoplastic left heart syndrome. A total of 232 holes were generated in 40 pieces of excised porcine atrial wall by a 788 kHz single-element transducer. The effects of various parameters [e.g., pulse repetition frequency (PRF), pulse duration (PD), and gas content of liquid] on the erosion rate and energy efficiency were explored. An Isppa of 9000 W/cm2, PDs of 3, 6, 12, and 24 cycles; PRFs between 1.34 kHz and 66.7 kHz; and gas saturation of 40-55% and 79-85% were used. The results show that very short pulses delivered at certain PRFs could maximize the erosion rate and energy efficiency. We show that well-defined perforations can be precisely located in the atrial wall through the controlled ultrasound tissue erosion (CUTE) process. A preliminary in vivo experiment was conducted on a canine subject, and the atrial septum was perforated using CUTE.