Acute Efficacy Research Articles

Sustainability Strategies Of A 3-week Preventive Measure In Patients With Knee Osteoarthritis

Knee osteoarthritis as a degenerative joint disease is particularly relevant for occupational groups whose activities are associated with high loads or unfavorable postures over long periods of time. In the sense of effective secondary prevention, the BG Trauma Hospital of Hamburg uses a multimodal therapy concept, the so-called Kniekolleg. Data are now available for a two-year follow-up so that not only acute effects of the three-week start-up intervention, but also sustainability effects for long-term exercise adherence after two refresher courses, each after 12 month, can be reported. PURPOSE: Craftsmen and workers in the construction industry are at an increased risk of developing knee osteoarthritis due to their work-related burdens. In order to maintain the ability to work, occupational co-operative measures for secondary prevention can be carried out (Kniekolleg). The aim was to evaluate the efficacy after two years, depending on the degree of exercise adherence. METHODS: In a repeated measurements design (T1 before, T2 after Kniekolleg, T3 after one year (first refresher), T4 after two years (second refresher)), 140 construction patients were assessed for their dynamic muscular strength (knee extension, 60°/s), their quality of life (SF-36) and their characteristics for knee osteoarthritis (WOMAC). They were evaluated using analyses of variances, whereby one group trained after the Kniekolleg in the gym with instruction (G1 n=63), one group completed a home training program (G2 n=38) and one group did not train (G3 n=39). RESULTS: For all parameters, significant acute efficacy and 2-year sustainability effects were observed (p≤0.05, d: 0.2-0.8). There was no interaction with adherence during training after the Kniekolleg (p> 0.05). CONCLUSION: The Kniekolleg has proved to be effective in the long term, with a critical questioning of future research, why there are no differences between guided, reduced or even missing long-term maintenance training.

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei.

Background Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. Objectives The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. Materials and Methods Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. Results Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 μg/mL to 5.886 μg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50 = 0.809 μg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. Conclusion The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.

Catheter Ablation for Treatment of Atrial Fibrillation and Supraventricular Arrhythmias Without Fluoroscopy Use: Acute Efficacy and Safety.

ResumoFundamento O uso da radiação ionizante em procedimentos médicos está associado a riscos significativos à saúde dos pacientes e da equipe de saúde.Objetivos Avaliar a segurança e a eficácia aguda da ablação por cateter para tratamento da fibrilação atrial (FA) e arritmias supraventriculares (SVTs), utilizando uma abordagem exclusivamente não fluoroscópica, guiada por eco intracardíaco (ICE) e mapeamento 3D.Métodos 95 pts (idade média 60 ± 18 anos, 61% do sexo masculino) programados para ablação de FA (69 pts, 45 FA paroxística e 24 FA persistente) ou SVTs (26 pts – 14 reentrada nodal, 6 Wolf-Parkinson-White [WPW], 5 flutter atrial direito [AD], 1 taquicardia atrial). Nove pacientes (9,5%) tinham marcapasso definitivo ou dispositivos de ressincronização com desfibrilador. Dois sistemas de mapeamento eletroanatômico foram utilizados – CARTO (65%) e NAVx (35%), bem como cateteres de ICE disponíveis – Acunav e ViewFlex.Resultados O isolamento das veias pulmonares (VPs), bem como todos os outros alvos que precisavam de ablação em ambos os átrios, foram alcançados e adequadamente visualizados. Não foram observados derrames pericárdicos, complicações trombóticas ou outras intercorrências nesta série. Punções transseptais difíceis (19 pacientes – 20%) foram realizadas sem fluoroscopia em todos os casos. Não foi utilizada fluoroscopia de backup, e nenhum vestuário de chumbo foi necessário. Avaliações detalhadas dos marcapassos após o procedimento não mostraram nenhum dano aos eletrodos, deslocamentos ou mudanças de limiar.Conclusões Uma estratégia de ablação por cateter sem uso de radiação para FA e outras arritmias atriais é segura e eficaz quando guiada pela utilização adequada do ICE e do mapeamento 3D. Diversos sítios em ambos os átrios podem ser alcançados e adequadamente ablacionados sem a necessidade de fluoroscopia de backup. Não foram observadas complicações. (Arq Bras Cardiol. 2020; 114(6):1015-1026)

Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia

Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC’s anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC’s cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC’s anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia.

1249Acute efficacy and safety of pulmonary vein isolation for atrial fibrillation in patients alternatively assigned to high power short duration (70W, 8s) vs lesion index guided (35W) ablation

Abstract Background permanent trans-mural lesions not affecting surrounding anatomical structures is the goal of safe and effective wide antral pulmonary vein (PV) isolation in patients with paroxysmal and persistent atrial fibrillation (AF) undergoing catheter ablation (CA). Time, energy and contact force are parameters related to lesion goodness and incorporated in a complex formula (i.e. the lesion index, LSI™, Abbott). This parameter is emerging as the gold standard for PV isolation. Recently, the shallower but wider lesions created by high power short duration (HPSD) ablation has came to attention. Purpose to compare acute reconnection rate, procedural parameters, and complication rates in patients with paroxysmal or persistent AF undergoing CA. Methods one-hundred patients with paroxysmal and 100 with persistent AF will be alternatively assigned to undergo PV isolation with the FlexAbility™ (HPSD group, 70W, 41°, 8 seconds) or the TactiCath™ (LSI-group: 35W, 41°, LSI: 5-5.5 posterior wall, up to ≥6 anywhere else) catheter. A 3-D mapping system (Ensite Precision™) and a steerable sheath (Agilis™, both Abbott) were always used. Adenosine (30mg) is given after PV isolation and ≥ 20 minutes waiting time. Posterior wall isolation was added in all, and patients with persistent AF were additionally treated with mitral and cavotricuspid isthmus ablation. Results: between June and October 2019, 71 patients (68 ± 10 years old, 32 (45%) female, 44 (60%) paroxysmal AF, AF duration 58 ± 81 months) were alternatively assigned to HPSD (36, 51%) or LSI-guided (35, 49%) ablation. No difference in clinical characteristics was found between groups. After 44 ± 18 and 30 ± 14min of procedural and RF time, all PVs were isolated, and all 17 (24%) reconnections treated with an additional 4 ± 3 and 3 ± 2min, respectively. In 8 ± 3 and 7 ± 3 min of procedural and RF time, the PW was successfully isolated in all. PV isolation (34 ± 12min vs. 56 ± 16min; P<.0001), RF (18 ± 5min vs. 41 ± 9min; P<.0001), and total procedural (138 ± 34min vs. 162 ± 34min; P=.0026) time were shorter in the HPSD group. X-Ray time and effective dose did not differ. A similar rate of acute reconnections (9, 25% vs. 8 23%) was found when HPSD and LSI were compared. A higher, although statistically not significant, number of steam pops was observed in the HPSD (14, 39%) vs. LSI (8, 23%) group, possibly related to the higher incidence of moderate pericardial effusion (>0.5mm, <20mm) found the day following the ablation (10, 28% vs. 2, 6%; P=.0238). No further complications related to CA were detected. Conclusions in patients with paroxysmal and persistent AF undergoing their first CA, HPSD ablation is faster than an LSI-guided approach. Acute efficacy (reconnection rate) is similar. Although a higher rate of haemodynamically non-relevant pericardial effusions were seen in the HPSD group, these were all treated medically and the general safety profile of this approach is excellent and comparable to LSI ablation.

1242The flexibility, ease of using, and leaving curve of a standardized ablation index workflow for catheter ablation of paroxysmal atrial fibrillation

Abstract Background/Introduction The ‘CLOSE’ protocol, incorporating standardized ablation index (AI) targets in conjunction with defined inter-tag distance (ITD) has been shown to improve the acute and long-term success of pulmonary vein isolation (PVI) when treating paroxysmal atrial fibrillation (PAF). The reproducibility and learning curve for this protocol has not been studied. Purpose To assess the acute and long-term efficacy of CLOSE PVI across multiple operators (n = 37) in the 17-centre European study ‘VISTAX’. Methods 329 patients with PAF (61.8% male, 61.3 ± 10.1 years) underwent PVI according to the CLOSE protocol, with target AI values for each lesion of ≥400 on the posterior wall and ≥550 on the anterior wall, and target ITD of ≤6mm. Each 3-dimensional electroanatomic map was evaluated at a core lab where adherence to each of these criteria was assessed. 281/329 patients (85.1%) fulfilled all standardized workflow requirements and were adjudicated as having their PVI per-protocol (PP). First pass PVI and acute effectiveness (adenosine-proof first pass PVI at 30-minute challenge) were recorded. Clinical effectiveness was assessed as freedom from atrial arrhythmia recurrence through 12 months recorded via transtelephonic monitoring (weekly and symptomatically), in addition to holter and electrocardiogram monitoring during 3,6,12 month follow up visits. Learning curve analysis was evaluated on all investigators. Results First pass PVI rates were similar in the overall (86%) and PP cohorts (85%), as was acute effectiveness (82% in both cohorts). Freedom from atrial arrhythmia at 12 months too was identical for both cohorts (79%). Total procedure time and total ablation time decreased by an average 8 minutes and 10 minutes respectively after the first procedure and then showed further steady decreases over the number of ablations performed by the investigator (Figure). The procedural efficiencies and clinical success were reproducible across different centers. No significant deviations were found from individual sites. Conclusion The standardized CLOSE workflow is reproducible across centres, and is ‘forgiving’ without impacting on high efficacy of almost 80%. The learning curve is short, suggesting that the excellent clinical results can be replicated widely and easily. Abstract Figure. Learning Curves- Procedure & Ablation

P1149Subcutaneous implantable cardioverter-defibrillator when Transvenous ICD is not a viable option

Abstract Funding Acknowledgements NO FUNDING OnBehalf RHYTHM DETECT Registry Background The class of recommendation for S-ICD implantation in patients who have inadequate vascular access is I according to AHA-ACC-HRS Guidelines and IIb according to ESC Guidelines. Data are lacking about the use of S-ICD for patients in which a transvenous ICD is not a viable option because of the inability to deploy a transvenous lead. Purpose To describe current practice and to measure outcomes associated with S-ICD use in patients in which a transvenous ICD is not a viable option. Methods 942 consecutive patients underwent S-ICD implantation at 22 Italian centers from 2014 to 2019. We identified 101 (11%) patients who received S-ICD because of the reported impossibility of deploying a transvenous lead. Results 21 patients presented with inadequate vascular access but no previous device in place. One patient had a mechanical prosthesis in tricuspid position. The remaining 79 patients received the S-ICD after removal of a prior system implanted, and venous occlusion was diagnosed after lead extraction, or partially or completely failed lead removal. In 24 of these patients a functional transvenous pacing system was left in place for persisting pacing needs. Patients were 60 ± 15 years old, 85% were male, 77% had ischemic or non-ischemic dilated cardiomyopathy, ejection fraction was 36 ± 13%. At implantation, acute conversion test was performed in 64 patients and shock energy of ≤65J was successful in 62 (96.9%) patients. During a median follow-up of 18 months, 6 patients died for non-device related reasons and 1 patient underwent heart transplantation. One patient underwent device replacement for battery depletion and one patient underwent leadless pacemaker implantation. Minor complications (hematomas not requiring system revision) were reported in 2 patients. Appropriate therapies were delivered in 4 patients and 8 patients experienced inappropriate therapies (in 3 patients due to double counting during pacing); all resolved with device reprogramming. Conclusions: In current clinical practice, a minority of S-ICD patients receive the device because of inadequate vascular access. The profile of these patients is similar to that of the typical ICD population in the context of primary sudden death prevention, but many of them present with pacing indications. Acute and mid-term efficacy of S-ICD seemed high. Few complications occurred during follow-up. Particular attention must be paid to device programming for those patients with concomitant pacing systems, in order to prevent inappropriate therapies.

P1055Reduction of radiation exposure using an optimized fluoroscopy protocol in cryoballoon ablation does not compromise clinical outcome

Abstract Background/Introduction Pulmonary vein isolation (PVI) using cryoballoon (CB) ablation is associated with an increased radiation exposure compared to radiofrequency ablation. Previous studies showed that radiation exposure in CB PVI can be reduced by optimizing the fluoroscopy protocol without comprising acute efficacy and safety. Purpose We evaluated the mid-term outcome of an optimized fluoroscopy protocol in patients undergoing CB PVI. Methods The study population comprised 90 consecutive patients who underwent second generation CB-based PVI. The first 46 patients underwent CB PVI with conventional fluoroscopy settings (Group A). In the following 44 patients (Group B) an optimized fluoroscopy protocol was applied consisting of 1) using fluoroscopy instead of filming for determining the pulmonary vein occlusion grade; and 2) optimal collimation of the area of interest. Primary endpoints were the total dose area product (DAP), fluoroscopy time and freedom from documented recurrence of atrial fibrillation (AF) after a single procedure. Results Group B had a lower median DAP (1393 cGycm2 vs. 3232 cGycm2, P < 0.001) and median fluoroscopy time (20 min vs. 24 min, P < 0.001) as compared to group A. The 1-year freedom from documented recurrence of AF after a single procedure was similar among groups (74% in Group A vs. 77% in Group B, P = 0.71). There were no significant differences between both groups for the secondary endpoints, including procedure duration, proportion of patients with complete electrical isolation, and complications. Conclusion Using an optimized fluoroscopy protocol in CB PVI radiation exposure could be reduced with a similar 1-year clinical outcome.

P1453Feasibility and safety of a minimal fluoroscopy approach, aiming to ALARA strategy, compared to conventional approach in a population of adult patients with high risk accessory pathways

Abstract Funding Acknowledgements None Introduction Catheter ablation is the treatment of choice for accessory pathways (AP) in high risk patients.Traditionally fluoroscopy has been the primary tool for visualizing catheter position and stability, however it has been shown that 3D electro-anatomic mapping systems (3D EAMS) can significantly reduce and even eliminate fluoroscopy exposure during catheter ablation, thus reducing the stochastic risk of malignancies. Purpose aim of our study is to assess that an ablation strategy using 3D EAMS with limited or no fluoroscopy, rigorous set-up of the X-ray equipment and intracardiac or transesofageal (TEE)echo to guide the transeptal puncture has the same degree of safety and effectiveness in ablating APs as the conventional fluoroscopic approach (CFA), and can be adopted for both right and left sided APs in the adult population,reducing the effective doses. Methods our retrospective analysis included 60 consecutive-prospective enrolled adult patients with high-risk APs treated either with a CFA in IRCCS Policlinico San Matteo (Pavia) or with a 3 EAMS guided minimally fluoroscopic approach (MFA) in Klinikum Fuerth (Fuerth) between 01/2016 and 09/2019. Results the 2 groups were homogeneous and comparable for age,sex and numbers of right/left-sided SP. In the MFA group we demonstrated the safety and feasibility of a principally 3D EAMS guided ablation approach, having the same rate of acute ablation success,while obtaining a statistically different fluoroscopy exposure time (P <0.000), dosis-area product (P< 0.000) and effective dosis (P < 0.000) compared to the CFA group. (Table) Conclusions the radiation exposure risk is cumulative and lifelong. We demonstrated that to adopt a MFA increasing the use of 3D EAMS, fluoro optminization and of TEE guided transeptal is feasible and safe forAPs ablation in adults, which will benefit of a lower or even absent fluoroscopic exposure while having the same degree of safety and efficacy of a CFA. Results Conventional Fluoroscopic Approach Minimal fluoroscopic approach P Patient (N) 31 29 n.s. Right AP 10 6 n.s. Left AP 21 23 n.s. Acute Efficacy 27 (87%) 28 (96.6%) n.s. Complication 1 (3%) 0 n.s. Fluoroscopy Time (min) 43+/-32 1.8+/-3.8 0.000 DAP (microGray*m2) 15252+/-11132 56.8+/-135.6 0.000 Effective Dosis (mSv) 30.35+/-27.7 0.09+/-0.28 0.000 AP, accessory pathway; min, minutes.

A novel thrombin-based triagonist with diabetes-protective and weight-lowering potential

AimsTo investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors. Main methodsTriagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6. Key findingsTG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models. SignificanceLTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.

Balloon-Based Ablation Technologies.

Pulmonary vein isolation (PVI) is widely accepted as the mainstay of interventional treatment of atrial fibrillation. Ablation with radiofrequency (RF) point-by-point catheters is highly operator dependent and may fail because of ineffective lesions or gaps. Several balloon-based catheter ablation technologies have emerged as an alternative to effect PVI. Cryoballoon ablation is widely used, and current iterations of the technology show comparable acute and long-term efficacy to RF ablation. Techniques such as time to isolation have emerged to improve efficacy and safety. Laser balloon is a highly compliant variably sized balloon that has been validated as an effective strategy for PVI.

Novel mono-PEGylated dimeric GLP-1 conjugate with enhanced receptor activation and prolonged anti-diabetes efficacies

AimsTo design and evaluate novel mono-PEGylated dimeric GLP-1 conjugate with enhanced GLP-1 receptor activation and prolonged anti-diabetes efficacies. Main methodsAll these novel GLP-1 conjugates were produced by using solid-phase synthesis method and further specific cysteine–maleimide modification. In vitro GLP-1R activation assay was performed in CHO cells stably expressing human GLP-1 receptor. The binding affinity for human serum albumin (HSA) in vitro was also conducted using surface plasmon resonance measurement. Subsequently, selected GLP-1 conjugate was subjected to evaluate the acute and chronic efficacies in vivo. Key findingsFour novel glucagon-like peptide-1 (GLP-1) conjugates, termed DIG-1 to DIG-4, were designed and prepared with high purity. Moreover, DIG-1(PEG-5 kDa) and DIG-2 (PEG-10 kDa) exerted ~3-fold and ~2-fold higher potencies of GLP-1R activation than native GLP-1, respectively, and both obviously higher than the DIG-3 (PEG-10 kDa) and DIG-4 (PEG-30 kDa). Then DIG-2 exhibited better in vivo glucose-stabilizing and insulinotropic efficacies than DIG-1 by using multiple oral glucose tests (OGTTs) in SD rats. Furthermore, prolonged glucose-lowering ability of DIG-2 exhibited in hypoglycemic duration test and multiple OGTTs in diabetic db/db mice. Pharmacokinetic data of DIG-2 in cynomolgus monkeys revealed a half-life of ~97.2 h and ~120.4 h after a single subcutaneous (s.c.) administration at doses of 100 and 150 nmol/kg, respectively. Chronic treatment of DIG-2 in db/db mice for consecutive 8-week significantly ameliorate the diabetic symptoms including deteriorative % hemoglobin A1C (HbA1C), glucose tolerance and pancreatic function. SignificanceDIG-2, as a novel mono-PEGylated dimeric GLP-1 conjugate, holds enhanced receptor activation and prolonged anti-diabetes efficacies.

Reducing radiation exposure in second-generation cryoballoon ablation without compromising clinical outcome

PurposePulmonary vein isolation (PVI) using cryoballoon (CB) ablation is associated with an increased radiation exposure compared with radiofrequency ablation. Previous studies showed that radiation exposure in CB PVI can be reduced by optimizing the fluoroscopy protocol without comprising acute efficacy and safety. We evaluated the mid-term outcome of a modified fluoroscopy protocol in patients undergoing CB PVI.MethodsThe study population comprised 90 consecutive patients who underwent second-generation CB-based PVI. The first 46 patients underwent CB PVI with conventional fluoroscopy settings (group A, historic control group). In the following 44 patients (group B), a modified fluoroscopy protocol was applied consisting of (1) visualization of degree of PV occlusion only by fluoroscopy (no cine runs); (2) increased radiation awareness. Primary endpoints were the total dose area product (DAP), fluoroscopy time, and freedom from documented recurrence of atrial fibrillation (AF) after a single procedure.ResultsGroup B had a lower median DAP (1393 cGycm2 vs. 3232 cGycm2, P < 0.001) and median fluoroscopy time (20 min vs. 24 min, P < 0.001) as compared with group A. The 1-year freedom from documented recurrence of AF after a single procedure was similar among groups (74% in group A vs. 77% in group B, P = 0.71). There were no significant differences between both groups for the secondary endpoints, including procedure duration, proportion of patients with complete electrical isolation, and complications.ConclusionUsing a modified fluoroscopy protocol and increased radiation awareness, radiation exposure can be significantly reduced in CB PVI with a similar 1-year clinical outcome.

Tumor cell death in orthotopic breast cancer model by NanoALA: a novel perspective on photodynamic therapy in oncology.

Aim: Nano-5-aminolevulic acid (NanoALA)-mediated photodynamic therapy (PDT), an oil-in-water polymeric nanoemulsion of ALA, was evaluated in a murine model of breast cancer. Materials & methods: Analysis of ALA-derived protoporphyrin IX production and acute toxicity test, biocompatibility and treatment efficacy, and long-term effect of NanoALA-PDT on tumor progression were performed. Results: The nanoformulation favored the prodrug uptake by tumor cells in a shorter time (1.5h). As a result, the adverse effects were negligible and the response rates for primary mammary tumor control were significantly improved. Tumor progression was slower after NanoALA-PDT treatment, providing longer survival. Conclusion: NanoALA is a good proactive drug candidate for PDT against cancer potentially applied as adjuvant/neoadjuvant intervention strategy for breast cancer.

171 Buprenorphine – A Treatment for Psychic Pain and Suicidal Ideation?

Buprenorphine (BPN) is an opiate medication that is increasingly used in the management of Opioid Use Disorder and pain disorders. This case report highlights the acute efficacy of using buprenorphine-naloxone (BPN-NAL) to reverse anhedonia and suicidal ideation in an individual with OUD, chronic pain and severe suicide attempts.We present a case of a 39-year-old male with a history of bipolar disorder, several lethal suicide attempts and polysubstance abuse, who presented to the hospital after self-immolation, burning 45% total body surface area. He was admitted to the burn unit for three months, reporting continual anhedonia, suicidal ideation, and flashbacks of seeing and feeling himself on fire. He also endorsed chronic pain and hopelessness.Upon transfer to the behavioral health unit, his symptoms persisted, despite trials of quetiapine, mirtazapine, methadone, oxycodone and prazosin. In consultation with pain management, he was initiated on sublingual BPN-NAL 8mg-2mg treatment as a transition from methadone; he immediately reported improvement in depressive symptoms and a reduction in pain. He was titrated on BPN-NAL and continued to report diminished pain and resolution of depression. Furthermore, his irritability was lessened and he newly cooperated with staff, participating in unit activities. Upon discharge, he exhibited stable mood, adequate pain control and the elimination of suicidal thoughts as well as a proactive drive for substance abuse treatment.This case describes the significance of BPN on relieving psychic pain and stabilizing mood in a chronically suicidal patient. We speculate that BPN's pharmacokinetic properties terminate the cycle of short-term opioid-induced analgesia and euphoria with opioid withdrawal-induced hyperalgesia and dysphoria. This results in a steady treatment of pain, as well as maintaining the dopaminergic system, symptomatically translating to mood stabilization and annulling suicidal ideation.

Meta-analysis of pulmonary vein isolation ablation for atrial fibrillation conventional vs low- and zero-fluoroscopy approaches.

Radiation exposure during catheter ablation procedures is a significant hazard for both patients and operators. Atrial fibrillation (AF) ablation procedures have been historically associated with higher fluoroscopy usage than other electrophysiology procedures. Recent efforts have been made to reduce dependence on fluoroscopy during pulmonary vein isolation (PVI) ablation procedures using alternative techniques. We performed a meta-analysis of studies comparing zero or low fluoroscopy (LF) vs conventional fluoroscopy (CF) approaches for AF ablation. Outcomes of interest included acute and 12-month procedural efficacy, safety, procedure duration, fluoroscopy time, and dose area product. Aggregated data were analyzed with random-effects models, using a Bayesian hierarchical approach. A total of 2228 participants (LF, n = 1190 vs CF, n = 1038) from 15 studies were included in the meta-analysis. Risk of AF recurrence in 12 months (odds ratio [OR], 95% confidence interval [95% CI] = 1.343 [0.771-2.340]; P = .297), redo-ablation procedures (OR [95% CI] = 0.521 [0.198-1.323]; P = .186), and procedural complications (OR [95% CI] = 0.99 [0.485-2.204]; P = .979) were similar between LF- and CF-ablation groups. In comparison to CF ablation, LF ablation led to shorter procedure duration (weighted mean differences [WMDs] [95% CI] = -14.6 minutes [-22.5 to -6.8]; P < .001), fluoroscopy time (WMD [95% CI] = -8.8 minutes [-11.9 to -5.9]; P < .001), and dose area product (WMD [95% CI] = -1946 mGy/cm2 [-2685 to 1207]; P < .001). LF approaches have similar clinical efficacy and safety as CF approaches for PVI. LF approaches are associated with shorter procedure time, fluoroscopy usage, and dose area product during PVI.

The Efficacy and Safety of Radiofrequency Catheter Ablation for Cardiac Arrhythmias in Pediatric Patients.

We aimed to evaluate the acute and long-term efficacy and safety of radiofrequency catheter ablation (RFCA) in Chinese pediatric patients with arrhythmias. We gathered clinical data from pediatric patients who underwent RFCA in several large medical centers in China between 2000 and 2019. A total of 4,622 different substrates in 4,622 patients were ablated, with the majority consisting of supraventricular tachycardia (N = 3,831, 82.9%) and ventricular arrhythmias (VAs) (N = 791, 17.1%). The majority of supraventricular tachycardia (SVT) consists of atrioventricular reentry tachycardia (AVRT) (N = 2,492, 65.0%) and atrioventricular nodal reentry tachycardia (AVNRT) (N = 1,075, 28.1%). The accessory pathway location was left-sided in 1,237(49.7%) and right-sided in 1,251(50.3%) of the 2,488 pathways. The VAs consist of premature ventricular contraction (PVC) (N = 597, 75.5%) and ventricular tachycardia (VT) (N = 194, 24.5%). The duration of follow-up ranged from 1 month to 1 year. The overall acute/long-term success rate of RFCA was 96.4%/92.2%, AVRT 97.8%/93.5%, AVRT 99.3%/95.0, PVC 98.1%/92.2%, and VT 81.3%/75.2%. Serious complications occurred in 29 patients (0.6%). This present study shows that RFCA is effective and safe in the treatment of arrhythmias in Chinese pediatric patients, with a high success rate exceeding 90%, low recurrence rate, and significantly reduces the risk of complications. The success rate of left-sided pathway ablation is slightly higher than that of the right-sided pathway. There is no difference in the success rate of RFCA among children of different ages. It could be the first-line therapy in the majority of pediatric patients with SVT and/or VAs.

Feasibility, safety, and acute efficacy of the fourth-generation cryoballoon for ablation of atrial fibrillation: Another step forward?

BackgroundThe second‐generation cryoballoon (CB2) is widely used for pulmonary vein (PV) isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). Recently, the novel fourth‐generation CB (CB‐Advance PRO) was introduced, incorporating a shortened catheter tip.HypothesisThe aim of this study was to evaluate the feasibility and acute efficacy of PVI using the CB‐Advance PRO.MethodsA total of 200 consecutive patients were analyzed. Hundred patients who underwent PVI due to symptomatic, drug‐refractory AF were treated with the CB‐Advance PRO (group I) and were included into this multicenter analysis. A group of 100 patients were treated with the CB2 and acted as controls (group II).ResultsIn total, 739 of 739 PVs (100%) were successfully isolated. There was a nonsignificant trend in the incidence of online registration of PV signals between both groups (group I: 77.9% vs group II: 71.4%, P = .09). Median time to PVI (time to isolation [TTI]) and mean total freezing time were significantly shorter when using the CB‐Advance PRO (group I: 33 [23, 50] vs group II: 40 [26, 60] seconds and group I: 166 ± 29 vs group II: 183 ± 38 seconds, P < .01). In three of 100 (3%) patients of group I and one of 100 (1%) patients of group II, a transient phrenic nerve palsy occurred (P = .62).ConclusionThe use of the novel CB‐Advance PRO is feasible and associated with a significant reduction in mean TTI and mean total freezing time as compared to the CB2.

Acute Safety and Efficacy of Fluoroless Cryoballoon Ablation for Atrial Fibrillation.

Pulmonary vein isolation (PVI) is widely used for the ablation of atrial fibrillation, with prior reports suggesting good efficacy. Due to the widespread use of three-dimensional electroanatomic mapping systems and advances in intracardiac echocardiography, fluoroless ablation has been made possible. Fluoroless ablation with a cryoballoon (CB), however, has not been widely performed because of the need to prove occlusion of the vein with contrast dye and fluoroscopy. The objective of this study is to show that CB ablation can be performed safely and effectively without fluoroscopy. A dual-center, case–control study was performed of patients undergoing CB PVI with a fluoroless approach and a control group with traditional fluoroscopic techniques. The absence of color-flow Doppler signals around the periphery of the CB on intracardiac echocardiography and an increase in mean pressure by 5 mmHg, loss of the A-wave, and an increase in the V-wave as measured with continuous-wave pressure monitoring were adopted as indicators of vein occlusion in the absence of fluoroscopy. Temperature at 30 seconds, minimum temperature, time to isolation, procedure length, and complications were evaluated. During the study period of November 15, 2018 to November 15, 2019, a total of 100 patients underwent CB PVI at the participating centers. A total of 50 patients were enrolled in the fluoroless arm [35 men (70%), mean age: 64.9 ± 12 years, mean left atrium size: 44.2 ± 16 mL/m2, left ventricular ejection fraction: 61% ± 5%], while 50 patients were enrolled in the control arm with similar characteristics. Four hundred forty-one 441 PVs were evaluated in the study cohort compared to 339 PVs in the control arm. When comparing fluoroless and traditional techniques, the mean temperature at 30 seconds was −31.7°C ± 6°C versus −32.8°C ± 5°C (p = 0.037), the minimum temperature was −47.4°C ± 6°C versus −47.7°C ± 9°C (p = 0.677), the time to isolation was 56.8 ± 28 seconds versus 74.8 ± 45 seconds (p = 0.212), and the procedure time was 102.2 ± 27.3 seconds versus 104.5 ± 16.9 seconds (p = 0.6436). Ultimately, this proof-of-concept study revealed that fluoroless ablation can be performed with success and efficiency outcomes similar to those of a traditional ablation approach. This suggests that the ablation of atrial fibrillation with CB can be performed safely and effectively without the use of fluoroscopy by experienced operators.

Real-World Safety and Efficacy of Transcatheter Mitral Valve Repair With MitraClip: Thirty-Day Results From the Italian Society of Interventional Cardiology (GIse) Registry Of Transcatheter Treatment of Mitral Valve RegurgitaTiOn (GIOTTO)

BackgroundAvailable scientific evidence of transcatheter mitral valve repair with the MitraClip comes from randomized controlled trials, which showed controversial results that hardly translate into real-world practice, and from registries of relatively small sample size. AimTo collect real-world data in a multicenter, prospective, country-level registry. Methods and resultThe Italian Society of Interventional Cardiology (GIse) Registry Of Transcatheter Treatment of Mitral Valve RegurgitaTiOn (GIOTTO) is an ongoing single-arm, multicenter, prospective registry that started enrollment in February 2016. Clinical end points were defined according to the Mitral Valve Academic Research Consortium (MVARC) criteria. From February 2016 to December 2018, 1189 patients (mean age 76 ± 9.1 years) were enrolled. The main MR etiology was functional (64.9%). MVARC technical success was 96.6%. At 30-day follow-up (n = 1131), MVARC device and procedural success were 92.5% and 87% respectively, and all-cause death was 3%. The majority of patients who died at 30-day had functional MR (69.7%). Mixed etiology (OR 0.94, 95% CI 0.02–0.61) and prolonged length of stay in ICU (OR 0.97, 95% CI 0.95–0.99) were found to be negative independent predictors of device success at 30-day. The EuroSCORE II (OR 0.96, 95% CI 0.93–0.99), LVEDV-I (OR 0.99, 95% CI 0.98–0.99) and prolonged length of stay in ICU (OR 0.98, 95% CI 0.97–0.99) were negative independent factors of MVARC procedural success at 30-day. ConclusionsThe GIOTTO registry is one of the largest prospective registries available on MitraClip and shows favorable acute and 30-day safety and efficacy.