Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction

AbstractObjectivesThe objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BackgroundIncreased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity.MethodsPatients with New York Heart Association (NYHA) functional class III HF and ejection fractions ≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance.ResultsOne hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event–free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (–17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro–brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08).ConclusionsBAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro–brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160

Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry

Introduction The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. Methods We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View™; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. Results Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145–354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). Conclusions Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center’s first cases

Feasibility and Safety of Uninterrupted Rivaroxaban for Periprocedural Anticoagulation in Patients Undergoing Radiofrequency Ablation for Atrial Fibrillation Results From a Multicenter Prospective Registry

ObjectivesThe purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation.BackgroundOptimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown.MethodsWe performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period.ResultsA total of 642 patients were included in the study, with 321 in each group. Mean age was 63 ± 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 ± 1.0 vs. 1.47 ± 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days.ConclusionsUninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy

Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER

T-cell protein tyrosine phosphatase gives rise to two splice isoforms: TC48, which is localized to the endoplasmic reticulum (ER) and TC45, a nuclear protein. The present study was undertaken to identify proteins that are involved in targeting TC48 to the ER. We identified two TC48-interacting proteins, p25 and p23, from a yeast two-hybrid screen. p23 and p25 are members of a family of putative cargo receptors that are important for vesicular trafficking between Golgi complex and ER. Both p23 and p25 associate with overexpressed TC48 in Cos-1 cells as determined by coimmunoprecipitation. A significant amount of TC48 colocalized initially with ERGIC and Golgi complex markers (in addition to ER and nuclear membrane localization) and was then retrieved to the ER. Coexpression with p25 enhanced ER localization of TC48, whereas coexpression with p23 resulted in its trapping in membranous structures. Coexpression of a p25 mutant lacking the ER-localization signal KKxx resulted in enhanced Golgi localization of TC48. Forty C-terminal amino acid residues of TC48 (position 376-415) were sufficient for interaction with p23 (but not with p25) and targeted green fluorescence protein (GFP) to the Golgi complex. Targeting of GFP to the ER required 66 C-terminal amino acid residues of TC48 (position 350-415), which showed interaction with p25 and p23. We suggest that TC48 translocates to the Golgi complex along the secretory pathway, whereas its ER localization is maintained by selective retrieval enabled by interactions with p25 and p23

A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants

PURPOSE. Mutations in the coding region of the OPTN gene are associated with certain glaucomas. Although the function of the optineurin protein is yet to be elucidated, the most common mutation, E50K, is associated with a severe phenotype. This study explores some functional features of optineurin and its mutants. METHODS. Plasmids expressing normal or wild-type (WT) and E50K, R545Q, H26D, and H486R mutant optineurin were transfected into HeLa, Cos-1, IMR32, and the rat retinal ganglion cell (RGC) line RGC-5, and their effects on cell survival monitored by morphologic observation of cells were studied. Expression of optineurin and its mutants was monitored by immunofluorescence staining of cells and by Western blotting. RESULTS. The E50K mutant of optineurin selectively induced the death of retinal ganglion cells but not of the other cell lines tested. Although the expression of optineurin and E50K mutant suppressed cell death induced by tumor necrosis factor-␣ in HeLa cells, they potentiated this cell death in retinal ganglion cells. Cell death induced by the optineurin mutant in retinal ganglion cells was inhibited by the antioxidants N-acetylcysteine and Trolox. Reactive oxygen species (ROS) were produced upon expression of E50K, which were reduced by antioxidants. Coexpression of manganese superoxide dismutase with the E50K mutant abolished ROS production and inhibited cell death. CONCLUSIONS. The E50K mutation of optineurin acquired the ability to induce cell death selectively in retinal ganglion cells. This cell death was mediated by oxidative stress. The present findings raise the possibility of antioxidant use for delaying or controlling some forms of glaucoma. (Invest Ophthalmol Vis Sci

A Robust Medical Image Watermarking Scheme Based on Nature-Inspired Optimization for Telemedicine Applications

Medical images and patient information are routinely transmitted to a remote radiologist to assist in diagnosis. It is critical in e-healthcare systems to ensure that data are accurately transmitted. Medical images of a person’s body can be used against them in many ways, including by transmitting them. Copyright and intellectual property laws prohibit the unauthorized use of medical images. Digital watermarking is used to prove the authenticity of the medical images before diagnosis. In this paper, we proposed a hybrid watermarking scheme using the Slantlet transform, randomized-singular value decomposition, and optimization techniques inspired by nature (Firefly algorithm). The watermark image is encrypted using the XOR encryption technique. Extensive testing reveals that our innovative approach outperforms the existing methods based on the NC, SSIM, and PSNR. The SSIM and NC values of watermarked image and extracted watermark are close to or equal to 1 at a scaling factor of 0.06, and the PSNR of the proposed scheme lies between 58 dB and 59 dB, which shows the better performance of the scheme