PV Isolation Using a Spherical Array PFA Catheter: Application Repetition and Lesion Durability (PULSE-EU Study).

BACKGROUND: Preclinical studies have revealed that pulsed field ablation (PFA) lesion dimensions increase with repetitive applications at a similar electric field. OBJECTIVES: This study investigated whether pulmonary vein isolation (PVI) durability varies with single vs repetitive pulsed field (PF) applications. METHODS: Atrial fibrillation patients underwent PVI using a spherical multielectrode array PFA catheter delivered with a 19-F deflectable sheath under intracardiac echocardiographic guidance. Esophagogastroduodenoscopy and brain magnetic resonance imaging were performed within 1 to 3 days, and invasive remapping at ∼2 to 3 months. RESULTS: The patient cohort (n = 21; age 63 ± 11 years; 67% women) underwent PVI in either of 2 groups: group 1 (n = 11)-single PF application/PV; and group 2 (n = 10)-3 PF applications/PV. In both groups, PVI was acutely successful in all (100%) patients. Despite significantly longer pulse delivery times (75.2 ± 7.4 s/patient vs 24.5 ± 5.5 s/patient) the procedure times (73.2 ± 13.7 minutes vs 93.7 ± 18.5 minutes) were shorter with group 2 vs group 1. There was no stroke/transient ischemic attack, pericardial effusion, phrenic nerve injury, or esophageal complications. Esophagogastroduodenoscopy was normal in both groups of patients (n = 9). Screening brain magnetic resonance imaging revealed asymptomatic cerebral lesions (diffusion weighted imaging+/fluid attenuated inversion recovery-) in 3 of 16 (18.7%) patients. PV remapping revealed durable PVI in 62.5% PVs in group 1 (n = 10), compared with all 100% PVs in group 2 (n = 9); this translates to all PVs being durably isolated in 30% vs 100% (P < 0.05) of patients in groups 1 and 2, respectively. CONCLUSIONS: In his first-in-human trial, the "single-shot" spherical array PFA catheter was shown to safely isolate PVs. Repetitive PF application is key for lesion consolidation to maximize PVI durability.

PV Isolation Using a Spherical Array PFA Catheter: Preclinical Assessment and Comparison to Radiofrequency Ablation.

BACKGROUND: A multielectrode spherical array catheter capable of single-shot mapping and ablation has been introduced. OBJECTIVES: This study sought to compare the efficacy and safety of circumferential, linear, and focal ablation using either microsecond pulsed field (PF) and radiofrequency (RF) ablation in preclinical model. METHODS: Under general anesthesia, a 122 gold-plated multielectrode array was introduced into the left atrium. Twenty-nine canines underwent isolation of two pulmonary veins (PVs), with linear and focal left atrial ablation with both RF (n = 12) and PF (n = 17). PF was also delivered within the superior vena cava and atop the esophagus in three swine. Animals were sacrificed acutely (immediately for RF [6 of 12] and 3 days for PF [6 of 17]) and the remaining (n = 17) at 14 to 30 days. Detailed necropsy and histopathology were performed. RESULTS: All PVs were acutely (58 of 58) and durably (34 of 34) isolated and exhibited wide confluent lesions. Lesions were transmural for 97% to 100% of sections with depths of 2.5 to 3.4 mm and 2.5 to 3.5 mm in the acute and chronic cohorts, respectively. Linear and focal lesions displayed transmurality rates of 85% to 100% with depths of 3.5 millimeters to 4.2 millimeters in the acute cohort. In the chronic cohorts, linear lesions created with RF, PF+RF, and PF had no significant differences in depth (3.5 ± 1.8 mm, 4.0 ± 1.4 mm, and 3.9 ± 0.9 mm) or transmurality (83.3%, 100%, and 80%). Current of injury was seen on local unipolar electrogram immediately after PF and RF, and this occurred to a wider extent with PF. PF but not RF elicited bradycardia from ganglionated plexi stimulation. There were no instances of phrenic palsy, venous stenosis, esophageal damage, or thromboembolism. CONCLUSIONS: Circumferential, linear, and focal mapping and ablation can be achieved with this novel catheter using both PF and RF, with excellent efficacy and safety.

Endobronchial cancer detection using an integrated bronchoscopy system for simultaneous imaging and noncontact spectral measurement.

INTRODUCTION: Quantitative spectroscopy has been proposed as a means of improving the specificity of autofluorescence bronchoscopy by discriminating between true malignancy and suspicious but benign lesions before biopsy. This study investigated the potential discrimination ability of microvascular tissue-related parameters and relative intensity of autofluorescence, as estimated by noncontact spectroscopy. METHODS: Patients undergoing bronchoscopy for suspicion of lung cancer were enrolled from 4 sites (Canada, Russia, Slovenia, and the United Kingdom). In lesions selected for biopsy, light from a special fiberoptic bronchoscope was diverted to a spectrophotometer to obtain spectral measurements. The mucosa blood volume fraction and oxygen saturation were estimated from the computer model and, along with the autofluorescence intensity, were analyzed for discrimination potential for severe dysplasia or worse against lower histology grades. RESULTS: A total of 485 patients were enrolled, from whom 352 suspicious, adequate biopsy specimens were collected. Of these, 8 specimens were severe dysplasia or carcinoma in situ, and 66 were cancer. All measures were found to be significantly altered (receiver operating characteristic curve area: 0.83, 0.74, and 0.80 for autofluorescence intensity, the blood volume fraction, and oxygen saturation, respectively) in lesions found by biopsy to have severe dysplasia or higher grade present. In addition, the estimated volume fraction of desaturated blood was found to be significantly more discriminatory than that of oxygen-saturated blood (receiver operating characteristic curve area: 0.83 vs. 0.63). Study center differences were evident and suggest that results may depend on study population or bronchoscopist experience. CONCLUSIONS: Noncontact measurement and estimation of the above microvascular-related parameters, obtained during regular bronchoscope examination, may have potential for improving discrimination of severe dysplasia and cancer in lesions suspicious under white light bronchoscopy/autofluorescence bronchoscopy.

Detection of lung cancer by automated sputum cytometry.

INTRODUCTION: Biomarkers may prove to be valuable tools to manage those at risk of lung cancer. Sputum analysis using DNA cytometry has shown promise, but an automated, objective sputum analysis test has yet to be developed. This study evaluated the performance characteristics of the LungSign test for lung cancer and compared them to conventional cytology METHODS: A multicenter validation trial was conducted in which sputum specimens were prospectively collected from subjects suspected of having lung cancer during diagnostic workup. Specimens were placed on slides, DNA stained using Feulgen thionin, and analyzed using an automated cytometry-based scoring system. Smears were also prepared from the sputum specimens, stained by the Papanicolaou procedure, and analyzed using conventional cytology. LungSign scores and conventional cytology results were compared with the subject diagnoses. RESULTS: A total of 1235 high-risk subjects were enrolled at nine clinical sites. Of 1123 subjects included for analysis, 370 were found to have lung cancer--a 33% prevalence. The a priori selected LungSign score threshold detected 40% of all lung cancers and 35% of stage I lung cancers with 91% specificity. Test performance was statistically equivalent across cancer stages, histologic types, and localizations for 330 analyzable lung cancer subjects. LungSign receiver operating characteristic area under the curve measure for the test was 0.692. Conventional cytology detected 16% of lung cancers with 99% specificity. CONCLUSIONS: DNA cytometry of sputum using the LungSign test detects stage I lung cancer and may provide a new tool to manage high-risk individuals.

Endometrial thermal balloon ablation using a high temperature, pulsed system: a mathematical model.

A new endometrial thermal balloon ablation treatment for menorrhagia is modeled mathematically to predict its efficacy and safety. A device preheats a fluid to 173 degrees C within a reservoir external to the uterus, and then pulses this fluid without further heating between the reservoir and the balloon for 2.1 min of treatment time. The model predicted this treatment to result in consistent immediate tissue death (coagulation) depths of 3.4 +/- 0.1 mm for uterine cavities of 7 to 26 mL, and that eventual necrosis (tissue death that would occur 1-5 days post burn) may occur to depths of 6.5 +/- 0.2 mm. Whereas, burn depths varied with uterine cavity volume when a low temperature treatment (constant 75 degrees C for 15 min) was modeled (2.3-2.9 mm and 6.8-8.2 mm, for immediate tissue death and eventual necrosis respectively). Similarly, the high temperature, pulsed treatment was less sensitive to blood perfusion rate than the low temperature treatment. Predicted eventual necrosis depth was 1.5 mm less for the high temperature, pulsed treatment than that predicted for a low temperature treatment (constant 87 degrees C for 7 min) for the same immediate tissue death depth (3.5 mm), indicating that the new high temperature treatment may result in less damage to non targeted tissues.