Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety, and Durability.

BACKGROUND: Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine. METHODS: A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Predetermined survival periods were <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanasia. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination. RESULTS: All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm; P=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14-28 days), all animals demonstrated significant esophageal healing-8 with complete resolution, and 2 with only trace fibrosis. CONCLUSIONS: A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.

Drug-coated balloon strategy following orbital atherectomy for calcified coronary artery compared with drug-eluting stent: One-year outcomes and optical coherence tomography assessment.

BACKGROUND: Percutaneous coronary intervention (PCI) for calcified coronary artery remains challenging in the drug-eluting stent (DES) era. While recent studies reported the efficacy of orbital atherectomy (OA) combined with DES for calcified lesion, the effectiveness of drug-coated balloon (DCB) following OA has not been fully elucidated. METHODS: Between June 2018 and June 2021, 135 patients who received PCI for calcified de novo coronary lesions with OA were enrolled and divided into two groups; OA followed by DCB (n = 43) if the target lesion achieved acceptable preparation, or second- or third-generation DESs (n = 92) if the target lesion showed suboptimal preparation between June 2018 and June 2021. All patients underwent PCI with optical coherence tomography (OCT) imaging. The primary endpoint was 1-year major adverse cardiac event (MACE), that was a composite of cardiac death, nonfatal myocardial infarction, or target lesion revascularization. RESULTS: Mean age was 73 years and 82% was male. In OCT analysis, maximum calcium plaque was thicker (median: 1050 µm [interquartile range (IQR): 945-1175 µm] vs. 960 µm [808-1100 µm], p = 0.017), calcification arc tended to larger (median: 265° [IQR: 209-360°] vs. 222° [162-305°], p = 0.058) in patients with DCB than in DES, and the postprocedure minimum lumen area was smaller in DCB compared with minimum stent area in DES (median: 3.83 mm2 [IQR: 3.30-4.52 mm2 ] vs. 4.86 mm2 [4.05-5.82 mm2 ], p < 0.001). However, 1 year MACE free rate was not significantly different between 2 groups (90.3% in DCB vs. 96.6% in DES, log-rank p = 0.136). In the subgroup analysis of 14 patients who underwent follow-up OCT imaging, late lumen area loss was lower in patients with DCB than DES, despite lower lesion expansion rate in DCB than DES. CONCLUSIONS: In calcified coronary artery disease, DCB alone strategy (if acceptable lesion preparation was performed with OA) was feasible compared with DES following OA with respect to 1-year clinical outcomes. Our finding indicated using DCB with OA might be reduce late lumen area loss for severe calcified lesion.

Volumetric assessment of individual thalamic nuclei in patients with drug-naïve, first-episode major depressive disorder.

Introduction: Despite the previous inconsistent findings of structural and functional abnormalities of the thalamus in patients with major depressive disorder (MDD), the disruption of the thalamic nuclei in the pathophysiology of this disorder has not yet been adequately studied. Therefore, we investigated the volumetric changes of thalamic subregions and their nuclei in drug-naïve, first-episode MDD patients. We also investigated the association between HAM-D scores, a clinical scale frequently used to evaluate the severity of depression and thalamic nuclei volumes in MDD patients. Methods: This study included 76 drug-naïve MDD patients and an equal number of healthy subjects. Magnetic resonance imaging (MRI) data were obtained using a 3T MR system and thalamic nuclei volumes were evaluated using FreeSurfer ver.7.11. The volumetric differences were compared by one-way analysis of covariance (ANCOVA) and to ensure that effects were not accounted for by other factors, age, sex, and ETICV variables were included as covariates. Results: We observed significant volume reductions of the left whole thalamus (p < 0.003) and several thalamic nuclei mostly on the left side in the MDD group compared with healthy controls (HCs). Furthermore, we have revealed weak negative correlations between several thalamic nuclei volumes and HAM-D total and subscale scores. Discussion: This is the first research study to investigate alterations of the various thalamic nuclei volumes in MDD patients compared with HCs. Moreover, we first analyzed the association between individual thalamic nuclei volumes and HAM-D subscale scores. Though our study may be restricted at certain levels, especially by the demographic difference between the two groups, they possibly contribute at a preliminary level to understanding the thalamic structural changes at its subregions in patients with drug-naïve, first-episode MDD.

Assessment of the Safety and Efficacy of Edoxaban for the Treatment of Venous Thromboembolism Secondary to Active Malignancy.

Objective: To assess the safety and efficacy of edoxaban for the treatment of venous thromboembolism (VTE) secondary to active malignancy. Materials and Methods: We enrolled 48 patients with newly diagnosed VTE secondary to active malignancy that was treated with oral edoxaban for 1 year between September 2014 and August 2015. We retrospectively examined the presence or absence of recurrent symptomatic VTE, VTE-related mortality, and bleeding events. Results: No recurrent symptomatic VTE or VTE-related deaths were recorded, enabling efficient assessment. Treatment safety was determined based on the reports of bleeding. Bleeding was reported in two patients, with serious bleeding in one of them. Conclusion: Edoxaban is safe and effective for the treatment of VTE secondary to active malignancy.

Juxtacortical Lesions in Multiple Sclerosis: Assessment of Gray Matter Involvement Using Phase Difference-enhanced Imaging (PADRE).

PURPOSE: In multiple sclerosis (MS), a juxtacortical lesion at the border between the gray matter (GM) and subcortical white matter (WM) may often involve the GM. A recently developed, phase-weighted magnetic resonance imaging (MRI) technique "phase difference enhanced imaging (PADRE)" can delineate the GM and WM clearly due to the difference in myelin concentration. We evaluated whether PADRE is useful for the detection of GM involvement in the juxtacortical MS lesions. METHODS: One neuroradiologist reviewed the conventional MRI in 13 MS patients and selected 48 juxtacortical lesions. At the first reading session with the conventional MRI alone (T2-weighted imaging, and two-dimensional and three-dimensional fluid-attenuated inversion recovery), two other neuroradiologists classified the lesions into three patterns according to their anatomical locations: (a) subcortical WM lesions involving the subcortical WM alone; (b) intracortical (IC) lesions involving the GM alone; (c) mixed GM/subcortical WM (mixed) lesions involving the both subcortical WM and GM. We defined the subcortical WM as a WM within a distance of 10 mm from inner edge of the GM. For the analyses, we excluded the white matter lesions further than 10 mm from inner edge of the GM. At the second reading session MRI and PADRE were available and the radiologists re-evaluated their prior classification. RESULTS: At the first reading session, 27 lesions were classified as (a), 1 as (b), and 20 as (c). Therefore, a total of 21 lesions (44%) were judged to involve the GM. At the second reading session, the classification of 15 (31%) lesions changed; all 15 lesions were judged to involve the GM on the PADRE. Interobserver agreement (kappa value) was 0.84 for the first- and 0.95 for the second reading session. CONCLUSION: PADRE is useful for detecting GM involvement of the juxtacortical MS lesions.