Acute Efficacy Research Articles

Chloramine-T application for Trichodina sp. in Arapaima gigas juveniles: Acute toxicity, histopathology, efficacy, and physiological effects

Trichodinids are problematic ectoparasites for intensive arapaima fish farming, which can make their breeding costly and unprofitable. The search for effective and safe therapeutic molecules is constant, and chloramine-T has stood out as an effective biocide to treat various pathogens in aquaculture. Here we investigated the acute toxicity (LC50-4h) of chloramine-T and its behavioural, morphological, histological, physiological, and antiparasitic effects on the control of trichodinids in arapaima juveniles. Initially arapaima were exposed to chloramine-T (0, 10, 20, 40, 50, 60, 80, 100 mg L−1) for 4 h. During this period, behavioural, morphological, and mortality changes were recorded. Immediately after a toxicity test, gills were collected for the histological analysis. The LC50-4h was calculated at 23.8 mg L−1 of chloramine-T. Behavioural changes like erratic swimming, loss of balance, gasping at the water surface, excessive mucus, jumping at the water surface, lethargy and gill hyperventilation, and morphological changes like loss of scales, ocular opacity, and skin darkening, were considered mild in arapaima exposed to 10 and 20 mg L−1 of chloramine-T for 4 h. The arapaima gills exposed to 10, 20 and, 40 mg L−1 of chloramine-T presented epithelial hyperplasia, dilated venous sinus and eosinophilic infiltrate, but they were reversible and of a low pathological degree. Based on the acute toxicity test (LC50-4h) results, concentrations were defined for the in vivo efficacy test, during which arapaima were exposed to 0, 10, 15, and 20 mg L−1 of chloramine-T for 1 h. After a therapeutic bath, physiological and parasitological analyses were performed. The use of 20 mg L−1 of chloramine-T significantly reduced (p < 0.05) parasitism by Trichodina sp. with an efficacy of 50.27 % and 53.23 % in gills and on the body surface, respectively. Chloramine-T did not change haematological parameters (erythrogram and thrombogram) or the biochemical parameters of arapaima after 1 h of exposure. However, monocytosis and neutrophilia were noted at slightly higher concentrations (15 and 20 mg L−1), but changes in fish homeostasis were not characterised. Thus, we demonstrate that the application of a therapeutic bath with 20 mg L−1 of chloramine-T for 1 h reduces parasitism by trichodinids and does not affect general arapaima juvenile health.

A Retrospective Naturalistic Study Comparing the Efficacy of Ketamine and Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression.

Depression is a common mental disorder that affects many people worldwide, while a significant proportion of patients remain non-responsive to antidepressant medications. Alternative treatment options such as ketamine therapy and repetitive transcranial magnetic stimulation (rTMS) therapy are offered nowadays. This study aims to describe and compare the acute antidepressive efficacy of both, intramuscular ketamine and rTMS in depression patients seeking help in a naturalistic clinical mental health setting. The clinical records of 24 patients with treatment resistant depression were collected from the clinical base of a real life clinic. Twelve patients were treated with intramuscular ketamine, twice weekly for 8 sessions, and twelve patients were treated with 30 sessions of left dorsolateral prefrontal cortex – intermittent theta-burst stimulation (DLPFC-iTBS). Using three clinical assessments (HDRS, HAM-A, BDI-II), our data reveal that both therapies led to significant improvement in symptoms from pre- to post- treatment, as well as that the two experimental groups did not differ significantly with respect to pre- to post- depressive and anxiety symptoms, indicating that the effect of both experimental groups in our sample was equally effective. Furthermore, our results showed high remission and response rates in both groups, with no statistical differences between the patients of ketamine group and rTMS group in remission and response rates. We show a significant pre- to post- treatment reduction in depressive and anxiety symptoms, with no significant differences between the two experimental groups, indicating that the effect of both therapies was equally effective in our limited sample.

Phytochemical Profile, Safety and Efficacy of a Herbal Mixture Used for Contraception by Traditional Health Practitioners in Ngaka Modiri Molema District Municipality, South Africa.

The use of medicinal plants for contraception remains a common practice among South African ethnic groups. The present study assessed the phytochemical profile, cytotoxicity, acute oral toxicity and efficacy of a herbal mixture used for contraception by the Batswana of South Africa. An aqueous extract was prepared from equal quantities (in terms of weight) of Bulbine frutescens (roots), Helichrysum caespititium (leaves) and Teucrium trifidum (leaves) based on a recipe used by traditional health practitioners. The phytochemical profiles of the freeze-dried herbal mixture were analyzed using gas chromatography–mass spectrometry (GC-MS). In addition, cytotoxicity was determined using an MTT assay on Vero cells and in vivo contraceptive efficacy was evaluated using seven Sprague Dawley rats per control and treatment groups. The control group received distilled water while test groups received 5, 50 and 300 mg/kg of the herbal mixture, which was administered orally once a day for three consecutive days. Subsequently, female rats were paired 1:1 with males for 3 days. Their weights were measured weekly and incidence of pregnancy was recorded. The GC-MS chromatogram revealed the presence of 12 identified and 9 unidentified compounds. In terms of safety, the herbal mixture had an IC50 value of 755.2 μg/mL and 2000 mg/kg, which was the highest tested dose that caused no mortality or morbidity in the rats. A contraceptive efficacy of 14.5% was exerted with 50 mg/kg herbal mixture extract while other doses had no effects given that all the rats were pregnant. Based on a chi-square test (p < 0.05), there was no correlation between the tested herbal mixture doses and contraception, nor on the weight of the rats. Overall, the herbal mixture extract was found to be safe but had limited contraceptive efficacy at the tested doses. In future studies, exploring increased dose range, solvent extract types and hormonal analysis will be pertinent.

Acute efficacy of contiguous versus temporally discontiguous point-by-point radiofrequency pulmonary vein isolation in patients with paroxysmal atrial fibrillation: a randomized study.

Durable pulmonary vein (PV) isolation (PVI) determines the clinical success of catheter ablation for atrial fibrillation. In this randomized study, we investigated whether the temporally discontiguous deployment of ablation lesions adversely affected the acute efficacy of PVI. Thirty-six consecutive patients with drug-refractory paroxysmal atrial fibrillation (aged 59 ± 11, 58% males) were randomized 1:1 to either discontiguous (D-PVI) or contiguous (C-PVI) encircling radiofrequency (RF) lesions around ipsilateral PVs. A contact force-sensing catheter was used targeting a final interlesion distance < 6mm and the ablation index of 400-450 (anterior wall) and 300-350 (posterior wall). The study endpoint was defined as failure of first-pass PVI or acute PV reconnection during a waiting time (> 30min) followed by adenosine challenge. The total RF time, number of RF lesions, and mean interlesion distance were comparable in both groups. Total endpoint rates were 1/36 (3%) in the D-PVI vs 4/36 (11%) in the C-PVI groups; P = 0.34 for superiority, P = 0.008 for non-inferiority. Adenosine-induced reconnection of right PVs was the only endpoint in the D-PVI group. In the C-PVI group, first-pass PVI failed in 2 right PVs and spontaneous reconnection occurred in 2 other circles (left and right PVs). Temporally discontiguous deployment of RF lesions is not associated with lower procedural PVI efficacy when strict criteria for interlesion distance and ablation index are applied. The development of local edema around each ablation site does not prevent effective RF lesion formation at adjacent positions. clinicaltrials.gov (NCT03332862).

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups (P = .015), no significant difference was detected between the D and P groups (P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation.

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood.Methods: The role of tubular mitophagy in macrophage polarization upon high-dose ascorbate treatment was assessed by fluorescence-activated cell sorter analysis (FACS) in vitro and by immunofluorescence in AKI models of LPS-induced endotoxemia (LIE) from Pax8-cre; Atg7flox/flox mice. The underlying mechanisms were revealed by RNA-sequencing, gene set enrichment analysis (GSEA), luciferase reporter, chromatin immunoprecipitation (ChIP) and adeno-associated viral vector serotype 9 (AAV9) delivery assays.Results: High-dose ascorbate enables conversion of macrophages from a pro-inflammatory M1 subtype to an anti-inflammatory M2 subtype in murine AKI models of LIE, leading to decreased renal IL-1β and IL-18 production, reduced mortality and alleviated tubulotoxicity. Blockade of tubular mitophagy abrogates anti-inflammatory macrophages polarization under the high-dose ascorbate-exposed coculture systems. Similar abrogations are verified in LIE mice with tubular epithelium-specific ablation of Atg7, where the high-dose ascorbate-inducible renal protection and survival improvement are substantially weaker than their control littermates. Mechanistically, high-dose ascorbate stimulates tubular secretion of serpin family G member 1 (SerpinG1) through maintenance of mitophagy, for which nuclear factor-erythroid 2 related factor 2 (NRF2) transactivation is required. SerpinG1 perpetuates anti-inflammatory macrophages to prevent septic AKI, while kidney-specific disruption of SerpinG1 by adeno-associated viral vector serotype 9 (AAV9)-short hairpin RNA (shRNA) delivery thwarts the anti-inflammatory macrophages polarization and anti-septic AKI efficacy of high-dose ascorbate.Conclusion: Our study identifies SerpinG1 as an intermediate of tubular mitophagy-orchestrated myeloid function during septic AKI and reveals a novel rationale for ascorbate-based therapy.

Individualized or fixed approach to pulmonary vein isolation utilizing the fourth-generation cryoballoon in patients with paroxysmal atrial fibrillation: the randomized INDI-FREEZE trial.

AimsCryoballoon (CB) based pulmonary vein isolation (PVI) is a widely used technique for treatment of atrial fibrillation (AF); however the ideal energy dosing has not yet been standardized. This was a single-centre randomized clinical trial aiming at assessing the safety, acute efficacy, and clinical outcome of an individualized vs. a fixed CB ablation protocol using the fourth-generation CB (CB4) guided by pulmonary vein (PV) potential recordings and CB temperature.Methods and resultsPatients were randomized in a 1:1 fashion to two different dosing protocols: INDI-FREEZE group (individualized protocol): freeze-cycle duration of time to effect plus 90 s or interruption of the freeze-cycle and repositioning CB if a CB temperature of −30°C was not within 40 s. Control group (fixed protocol): freeze-cycle duration of 180 s. No-bonus freeze-cycle was applied in either patient group. The primary endpoint was freedom from atrial tachyarrhythmia at 12 months. Secondary end points included procedural parameters and complications. A total of 100 patients with paroxysmal AF were prospectively enrolled. No difference was seen in the primary endpoint [INDI-FREEZE group: 38/47 (81%) vs. control group: 40/47, (85%), P = 0.583]. The total freezing time was significantly shorter in the INDI-FREEZE group (157 ± 56 s vs. 212 ± 83 s, P < 0.001), while procedure duration (57.9 ± 17.9 min vs. 63.2 ± 20.2 min, P = 0.172) was similar. No differences were seen in the minimum CB and oesophageal temperatures as well as in periprocedural complications.ConclusionCompared to the fixed protocol, the individualized approach provides a similar safety profile and clinical outcome, while reducing the total freezing time.

The role of intracardiac echocardiography in reducing radiation exposure during atrial fibrillation ablation.

Intracardiac echocardiography (ICE) is a relatively young technique used during complex electrophysiology proce-dures, such as atrial fibrillation (AF) ablation. The aim of this study was to assess whether the use of ICE modifies the radia-tion exposure at the beginning of the learning curve in AF ablation. In this retrospective study, 52 patients, in which catheter ablation for paroxysmal or persistent AF was performed, were included. For 26 patients we used ICE guidance together with fluoroscopy, whereas for the remaining 26 patients we used fluoroscopy alone, all supported by electroanatomical mapping. We compared total procedure time and radiation exposure, including fluoroscopy dose and time between the two groups and along the learning curve. Most of the patients included were suffering from paroxysmal AF (40, 76%), pulmonary vein isolation being performed in all patients, without secondary ablation sites. The use of ICE was associated with a lower fluoroscopy dose (11839.60±6100.6 vs. 16260.43±8264.5 mGy, p=0.041) and time (28.00±12.5 vs. 42.93±12.7 minutes, p=0.001), whereas the mean procedure time was similar between the two groups (181.54±50.3 vs 197.31±49.8 minutes, p=0.348). Radiation exposure was lower in the last 9 months compared to the first 9 months of the study (p<0.01), decreasing gradually along the learning curve. The use of ICE lowers radiation exposure in AF catheter ablation from the beginning of the learning curve, without any difference in terms of acute safety or efficacy. Aware-ness towards closest to zero radiation exposure during electrophysiology procedures should increase in order to achieve better protection for both patient and medical staff.

Abstract 11445: Safety and Efficacy of Cryoballoon Ablation for Atrial Fibrillation Performed at Community Hospitals with Low to Medium Case Numbers: Acute and First Long Term Results of The German "Regional" Registry

Introduction: Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is a guideline recommended treatment for symptomatic paroxysmal and persistent atrial fibrillation. Little is known on performance data of CBA in low to medium volume hospitals. Hypothesis: To determine safety and efficacy of PVI using CBA performed at community hospitals with limited annual case numbers. Methods: This prospective registry included 1004 consecutive patients (pts) who had CBA performed for symptomatic paroxysmal (n=563) or persistent AF (n=441) at 20 hospitals, each with &lt;100 PVI / year. CBA procedures were performed according to local standards. Procedural data, efficacy and complication rates were determined. Results: The mean number of CBA / year / center was 59±25. CBA was performed by a total of 22 operators (1.1/center), 12/20 operators were board certified for invasive electrophysiology. Average procedure time was 90.1±31.6 min, fluoroscopy time was 19.2±11.4 min. Isolation of all pulmonary veins was reached in 97.9% of pts, the most frequent reason for not achieving complete isolation was development of phrenic nerve palsy (PNP). No hospital deaths were observed. 2 pts (0.2%) suffered a clinical stroke. Pericardial effusion occurred in 6 pts (0.6%), 2 (0.2%) required pericardial drainage. Vascular complications occurred in 24 pts (2.4%), 2 pts (0.2%) underwent vascular surgery. PNP occurred in 48 pts (4.8%) and persisted up to discharge in 6 pts (0.6%). The results were independant for board certification status of the operator and independant for the number of enrolled patients per center (if &gt; or &lt; 60 pts). Follow up data at 12 months were available from 14 centers and 75,2 % of their pts so far. Recurrent atrial arrhythmias after a 3 months blanking period were found in 177/536 pts. (33%), 152 (85,9%) were symptomatic. 71 (40%) pts with recurrence were still on antiarrhythmic drugs, 42 (23.7%) underwent Re-PVI. One phrenic nerve palsy persisted, there were no further access site complications and no esophago-atrial fistula. Conclusions: PVI for paroxysmal or persistant AF using CBA can be safely performed at community hospitals with high acute efficacy, low complication rates and good recurrence data after 1 year despite low and moderate annual case numbers.

Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter.

IntroductionThe AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface.MethodsWe evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter.ResultsA total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred.ConclusionThe AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.Supplementary InformationThe online version of this article (10.1007/s12471-021-01636-w) contains supplementary material, which is available to authorized users.

Third-generation laser balloon ablation for atrial fibrillation treatment: a multicenter experience

Abstract Background Laser balloon ablation is a promising option for performing pulmonary vein isolation (PVI) which is the cornerstone of invasive atrial fibrillation (AF) treatment. Purpose We aimed to investigate the acute efficacy and safety of the novel third-generation of the laser balloon system in an initial multicenter experience. Methods First and consecutive patients who underwent PVI with LB3 for drug-resistant paroxysmal or persistent AF at 7 Italian sites were included in this analysis. Study endpoints were acute procedural efficacy, defined as successful isolation of all identified PVs without radiofrequency touch-up, total and fluoroscopy times, and periprocedural complications. Results Our population included 86 patients (81% males, mean age 60.6±9.5 years) who underwent a procedure of PVI using LB3 between June 2020 and March 2021. Most patients had paroxysmal AF (74%) and were in sinus rhythm at the beginning of the procedure. The mean procedure time was 138±60 min; fluoroscopy time was 22±17 min and the mean ablation time was 44±40 min. Of the 313 targeted PVs, 311 (99.4%) could be isolated with first-pass LB3 application, while 2 (0.6%) required radiofrequency touchup. At the end of the procedure, all patients were in sinus rhythm and 26 (32%) received electrical cardioversion to achieve stable sinus rhythm. The total rate of major compilations was 1.2% (1/82 patients): one pericardial tamponade requiring epicardial puncture. No surgical intervention was necessary, and the patient recovered without any sequalae. There were no vascular access complications or phrenic nervy palsy. Three pinhole balloon raptures (3.5%) were observed during energy applications that required replacement of the whole system but had no effect on patient safety. Conclusions In a first multicenter experience, the LB3 system for PVI was safe with excellent acute efficacy. Funding Acknowledgement Type of funding sources: None.

Cryoballoon ablation of atrial fibrillation in low and medium volume hospitals – experiences of the German REGIONAL registry

Abstract Background Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) has become an established and widespread procedure for the treatment of symptomatic paroxysmal and persistent atrial fibrillation (AF). The safety and efficacy of PVI at low and medium volume hospitals is unknown. Aim To determine safety and acute efficacy of PVI using CBA performed at community hospitals with limited annual case numbers. Methods This registry study prospectively included 1004 consecutive patients who underwent PVI with CBA for symptomatic paroxysmal (n=563) or persistent AF (n=441) between 01/2019 and 09/2020 at 20 community hospitals (each performing &amp;lt;100 PVI/year). Qualifying criteria for participating hospitals were an experience of performing CBA for at least 1 year and a minimum of 50 CBA performed up to the start of the registry. All CBA procedures were performed according to the individual local standards of each hospital. Procedural data, acute efficacy and complications were determined. Results The mean annual number of CBA procedures performed was 59±26/hospital, the mean annual number of PVI performed regardless of the method used was 70±26/center. 8/20 hospitals performed CBA only. There were 22 operators (1,1/center), in 12/20 hospitals CBA was performed by an operator being board certified in invasive electrophysiology. 10/20 hospitals included &amp;lt;60 patients/center (n=381), the centers enrolling &amp;gt;60 patients/hospital included a total of 623 pts (62%). Mean procedure time was 90.1±31.6 min, mean fluoroscopy time was 19.2±11.4 min. Isolation of all pulmonary veins could be achieved in 97.9% of patients. Not achieving the goal of “all veins isolated” in a respective patient was mainly due to early termination of CBA procedure due to phrenic nerve palsy. Major complications occurred in 1,2% of patients: no in-hospital death (0%), clinical stroke in 2 patients (0.2%), pericardial effusion requiring pericardial drainage in 2 patients (0,2%), vascular complications needing vascular surgery and/or blood transfusion in 2 patients (0,2%), phrenic nerve palsy persisting up to hospital discharge in 6 patients (0,6%). Minor complications occurred in 7,5% of patients: pericardial effusion with no need of intervention in 0,4%, access site complications with no need for therapeutic intervention or prolonged in-hospital stay in 2,1% (mainly superficial hematoma) and phrenic nerve palsy resolving before discharge in 4,2%. No significant difference in the number of complications could be found when testing for numbers of enrolled patients (&amp;gt; or &amp;lt; than 60/hospital) or regarding the board certification status of the operator. Conclusions PVI for paroxysmal or persistent AF using CBA can be performed at community hospitals with high acute efficacy and low complication rates despite low and moderate annual procedure numbers. Funding Acknowledgement Type of funding sources: None.

Novel cryoballoon to isolate pulmonary veins in patients with paroxysmal atrial fibrillation: one-year outcomes in a multicenter study

Abstract Background Recently, a novel cryoballoon (CB; POLARx) has been developed with increased steerability which maintains size and pressure throughout the ablation. Initial clinical data has demonstrated acute procedural safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (AF). However, there are limited studies demonstrating the long-term efficacy of the CB. Purpose To evaluate the long-term safety and efficacy of the novel CB in treating paroxysmal AF. Methods This was a non-randomized, prospective, multi-center study. Fifty-eight consecutive patients with paroxysmal AF were enrolled at 4 centers for de novo PVI procedures. Cryoablation was delivered for 180s if time to isolation was ≤60s. Otherwise a 240s cryoablation was performed. PVI was confirmed with entrance and exit block testing. Patients were followed for 1 year with 24-hour Holter monitoring at 3, 6, and 12 months. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. Results Acute isolation with the CB was achieved in 230 of 231 pulmonary veins (99.6%) with 5.2±1.5 cryoapplications per patient (1.3±0.6 cryoapplications per vein). There were 4 patients (6.9%) with phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months follow-up). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post index procedure (1.7%). Of the 56 patients that had complete 12-month follow-up, 43 (76.8%) were free from recurrent atrial arrhythmias. Conclusion Initial multicenter clinical experience with the novel CB has demonstrated long-term safety and efficacy of PVI in patients with paroxysmal AF. Further studies are underway to confirm these findings. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boston Scientific

Examination of the acute efficacy and safety about aggressive use of tolvaptan for early rising after admission in super-elder patients with congestive heart failure

Abstract Background From August 2015, for shortening of hospitalization period through efficient medical care in acute phase, we had introduced a unique clinical pathway (PATH) for congestive heart failure (CHF) cases. In PATH, since immediate taking of Tolvaptan, which is an strong oral diuretic and approver for use in the treatment of CHF cases since 2010 in Japan, after admission is specified, early diuresis makes it possible to achieve early rising from bed and streamline each medical care such as oxygen inhalation, continuous infusion, and urethral catheterization. Early rising from bed is particularly important for super-elder CHF patients who merge often frail. On the other hand, for super-elder CHF patients, it is feared that aggressive use of Tolvaptan may frequently cause dehydration, renal damage caused by it, or hypernatremia, which is a peculiar side effect about the drug. Purpose In this study, we examined the usefulness and safety of active use of Tolvaptan by introducing PATH in patients with super-elder CHF patients. Methods We set up three groups, NE group consist of 37 CHF cases (90 years old or over) who admitted in our hospital before (without) introduction of PATH between April 2014 and July 2015, PE group consist of 130 CHF cases (90 years old or over) and PY group consist of 466 CHF cases (under 90 years old) who ware admitted with introduction of PATH between August 2015 and July 2020. And in each group, we investigated various medical conditions in their acute phase after admission and the incidence of adverse events related to oral administration of tolvaptan, and examined the differences between three groups. Results Between NE group and PE group, there were no significant differences in mean age, pre-hospital living status, or clinical status at admission (Figure 1). But due to lean and efficient CHF care, the average length of hospitalization period was significantly shorter in PE group. And, in PE group, each medical care was performed as efficiently as in PY group, but the progression of renal damage or hypernatremia that required unscheduled discontinuation of tolvaptan use occurred more frequently in PE group (Figure 2). Conclusions Aggressive Tolvaptan use through our unique clinical pathway for congestive heart failure cases seemed to be useful even in super-elder patients. Although we thought that the safety of active use of tolvaptan for super-elder patients was well tolerated considering the results of this study, the incidence of adverse events such as hypernatremia was clearly higher in super-elder patients than in non-super-elder patients. It seemed that we should pay close attention to the clinical data of super-elder patients after introduction of tolvaptan. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Accuracy and acute efficacy of a novel occlusion tool to guide cryoballoon-based pulmonary vein isolation

Abstract Background Cryoballoon (CB)-based pulmonary vein isolation (PVI) currently requires to verify occlusion of each pulmonary vein (PV) using fluoroscopy and dye injection. Objective The current study evaluated whether the novel CB-occlusion tool integrated into the wide-band dielectric imaging system KODEX-EPD reliably verifies occlusion of PV according to a novel dye-injection based algorithm. Methods Consecutive patients suffering from symptomatic atrial fibrillation (AF) underwent CB-based PVI using the KODEX-EPD and the novel occlusion-tool (group I). To confirm accurate display of the PVs, selective PV-angiography was performed in the first half of the patients of group I (group Ia) in addition to a three-dimensional left atrial (LA) map using a spiral mapping catheter (Achieve, SMC1, Medtronic, MN, USA). PV-angiographies were waived for the following patients (group Ib). Procedural duration and radiation exposure were compared to a control group of patients undergoing conventional CB-based PVI. Results CB-based PVI was successful in 50/50 patients of group I (mean age 63±11 years, 18 paroxysmal (36%)) and 25/25 patients of group II (66±10 years, 9 paroxysmal (60%)). Concordance of PV-occlusion as assessed by either PV-occlusion-angiography or KODEX-EPD, was documented in 237/272 (87%) occlusion-analyses among 198 PVs (95% for left superior PV, 93% for left inferior PV, 86% for right inferior PV and 77% for right superior PV). In the final evaluation phase (group Ib) LA fluoroscopy times and dose area products were comparable to the conventional CB-ablation group (10.5±5 vs 8.8±4 minutes (p=0.23) and 403±425 vs 321±202 cGycm2 (p=0.44), whereas the amount of dye could be significantly reduced (group Ib: 31±10 ml vs group II: 70±20 ml, p&amp;lt;0.0001). Conclusion The novel KODEX-EPD PV-occlusion tool allows for accurate PV-occlusion assessment in the majority of PVs and a high acute success rate. The system has the potential to reduce dye and radiation exposure. This should be evaluated in controlled clinical trials. Funding Acknowledgement Type of funding sources: None.

The role of local impedance drop in the acute lesion efficacy during pulmonary vein isolation performed with a new contact force sensing catheter-A pilot study.

IntroductionOur pilot study aimed to evaluate the role of local impedance drop in lesion formation during pulmonary vein isolation with a novel contact force sensing ablation catheter that records local impedance as well and to find a local impedance cut-off value that predicts successful lesion formation.Materials and methodsAfter completing point-by-point radiofrequency pulmonary vein isolation, the success of the applications was evaluated by pacing along the ablation line at 10 mA, 2 ms pulse width. Lesions were considered successful if loss of local capture was achieved.ResultsOut of 645 applications, 561 were successful and 84 were unsuccessful. Compared to the unsuccessful ablation points, the successful applications were shorter (p = 0.0429) and had a larger local impedance drop (p<0.0001). There was no difference between successful and unsuccessful applications in terms of mean contact force (p = 0.8571), force-time integral (p = 0.0699) and contact force range (p = 0.0519). The optimal cut-point for the local impedance drop indicating successful lesion formation was 21.80 Ohms on the anterior wall [AUC = 0.80 (0.75–0.86), p<0.0001], and 18.30 Ohms on the posterior wall [AUC = 0.77 (0.72–0.83), p<0.0001]. A local impedance drop larger than 21.80 Ohms on the anterior wall and 18.30 Ohms on the posterior wall was associated with an increased probability of effective lesion creation [OR = 11.21, 95%CI 4.22–29.81, p<0.0001; and OR = 7.91, 95%CI 3.77–16.57, p<0.0001, respectively].ConclusionThe measurement of the local impedance may predict optimal lesion formation. A local impedance drop > 21.80 Ohms on the anterior wall and > 18.30 Ohms on the posterior wall significantly increases the probability of creating a successful lesion.

Personalized paroxysmal atrial fibrillation ablation by tailoring ablation index to the left atrial wall thickness: the 'Ablate by-LAW' single-centre study-a pilot study.

To determine if adapting the ablation index (AI) to the left atrial wall thickness (LAWT), which is a determinant of lesion transmurality, is feasible, effective, and safe during paroxysmal atrial fibrillation (PAF) ablation. Consecutive patients referred for PAF first ablation. Left atrial wall thickness three-dimensional maps were obtained from multidetector computed tomography and integrated into the CARTO navigation system. Left atrial wall thickness was categorized into 1 mm layers and AI was titrated to the LAWT. The ablation line was personalized to avoid thicker regions. Primary endpoints were acute efficacy and safety, and freedom from atrial fibrillation (AF) recurrences. Follow-up (FU) was scheduled at 1, 3, 6, and every 6 months thereafter. Ninety patients [60 (67%) male, age 58 ± 13 years] were included. Mean LAWT was 1.25 ± 0.62 mm. Mean AI was 366 ± 26 on the right pulmonary veins with a first-pass isolation in 84 (93%) patients and 380 ± 42 on the left pulmonary veins with first-pass in 87 (97%). Procedure time was 59 min (49-66); radiofrequency (RF) time 14 min (12.5-16); and fluoroscopy time 0.7 min (0.5-1.4). No major complication occurred. Eighty-four out of 90 (93.3%) patients were free of recurrence after a mean FU of 16 ± 4 months. Personalized AF ablation, adapting the AI to LAWT allowed pulmonary vein isolation with low RF delivery, fluoroscopy, and procedure time while obtaining a high rate of first-pass isolation, in this patient population. Freedom from AF recurrences was as high as in more demanding ablation protocols. A multicentre trial is ongoing to evaluate reproducibility of these results.

AbsorbaSeal™ 5.6.7F vascular closure device: A good laboratory practice chronic study evaluating safety and efficacy in a healthy porcine model.

Vascular closure devices (VCDs) are widely used for arteriotomy closure after percutaneous catheter-based procedures. In comparison to manual compression, VCDs have been associated with shorter time to hemostasis, shorter time to ambulation, and also decreased length of stay. Complexity of deployment, lack of immediate hemostasis, and residual deformity of the arterial wall remain as limitations of current VCDs. The aim of this study was to investigate the AbsorbaSeal™ 5.6.7F vascular closure device, a novel, completely bioabsorbable, intuitive, and easy to use VCD which uses a compressive, "sandwich"-type design comprising a low profile intravascular distal seal and gasket and an extravascular floating foot and proximal seal, in an open infrarenal aortic swine model. Eight fully heparinized swine at a good laboratory practices facility underwent AbsorbaSeal™ 5.6.7F VCD closure of three 6F arteriotomies each in the proximal, mid, and distal infrarenal aorta. Two swine underwent harvest at each of four time cohorts: 30, 60, 90, and 120days. Acute and chronic procedural safety and efficacy, as well as target site vascular remodeling over time, were the primary outcomes evaluated. Secondary outcome measures included local and systemic inflammatory responses, end-organ tissue analysis, and device-related complications through the follow-up periods. Histopathological evaluation was performed by a blinded pathologist. Standard statistical methods were used. In deployment of 24 AbsorbaSeal™ 5.6.7F VCDs, there were no device-related complications or mortalities. All deployments resulted in rapid arteriotomy seal (100% deployment success), with a mean time to hemostasis (cessation of arterial flow) of 21.5s (median: 6.5s) across a mean activated clotting time (ACT) of 356s. Twenty of the 24 implant sites (83%) attained complete hemostasis within 20s. Immediate post-implant and pre-termination angiographies at all time points were performed of all swine which demonstrated normal aortic appearance and tissue structure and normal downstream vascular beds. At 30days, each implant's intravascular distal seal and gasket were removed from the circulation and completely covered with a smooth neointimal layer. Minimal inflammation and no intimal or luminal thrombus were observed at any site at every time point. AbsorbaSeal™ 5.6.7F is a safe, effective, and secure VCD that demonstrates rapid hemostasis in a fully heparinized open aortic porcine model. Removal from circulation and complete coverage of the intravascular distal seal and gasket with neointima occurred within 30days post-implant. Natural transmural vessel healing from the arteriotomy itself with minimal inflammation was noted for each implant at every time point.

Sleep Disorders in Pediatric Migraine: A Questionnaire-Based Study.

There is a high comorbidity between migraine and sleep disorders (SD), with a mutual dependence between sleep and headache. This study aimed to analyze the relationship between headache features (migraine frequency and severity, migraine equivalents, use and efficacy of treatments) and sleep in pediatric migraine. Parents of children and adolescents with migraine completed the Children’s Sleep Habits Questionnaire (CSHQ) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) and answered questions about headache characteristics. The presence of SD was defined according to CSHQ score. SD were detected in 72.9% of 140 subjects, but only 5.0% already received a diagnosis. Patients with SD presented statistically significant higher headache frequency (p = 0.031) and higher prevalence of migraine equivalents (p = 0.007). A higher CSHQ total score was associated with higher frequency of severe attacks (p = 0.012) and lower acute drug efficacy (p = 0.003). Significant positive correlations of sleep onset delay, sleep duration and nightwakings subscales with migraine frequency emerged. Our findings indicate that SD are highly prevalent in pediatric migraine and frequently associated with a higher headache severity and lower response to acute therapy, but often remain underdiagnosed. Improving sleep quality could help to reduce migraine intensity and disability and vice versa.

Technical and procedural comparison of two different cryoballoon ablation systems in patients with atrial fibrillation

PurposeThe aim was to report procedural and technical differences of a novel cryoballoon (NCB) ablation catheter for pulmonary vein isolation (PVI) compared to the standard cryoballoon (SCB) catheter.MethodsConsecutive patients with atrial fibrillation (AF) undergoing PVI using the NCB and the SCB were included. Procedural parameters, technical differences, acute efficacy, and safety are reported.ResultsEighty patients (age 66 ± 10 years, ejection fraction 57 ± 10%, left atrial volume index 40 ± 6 ml/m2) were studied. With the NCB, 156 of 158 PVs (99%) were isolated compared to isolation of 159 of 159 PVs (100%) with the SCB. The median number of freezes in the NCB and the SCB group was 6 (IQR 5–8) and 5 (IQR 4–7), respectively (p = 0.051), with 73% and 71% of the PVs isolated with a single freeze, respectively. Nadir temperature and temperature at isolation were − 59 ± 6 °C and − 45 ± 17 °C in the NCB group and − 46 ± 7 °C and − 32 ± 23 °C in the SCB group, respectively (both p < 0.001) with no difference in time to isolation (TTI). Procedural differences were observed for the total procedure time (84 ± 29 min in the NCB group and 65 ± 17 min in the SCB group, p = 0.003). There was a peri-procedural stroke in one patient in the NCB group. Differences in catheter design were observed that may account for the differences in temperature recordings and ice cap formation.ConclusionsAcute efficacy and TTI were similar with the NCB compared to the SCB. Measured temperatures were lower with the NCB, most likely due to differences in catheter design.