Left ventricular lead misplacement discovered a decade after cardiac resynchronization therapy-defibrillator implantation: a case report.

Introduction: Satisfactory left ventricular (LV) lead placement into the coronary sinus (CS) can be achieved in the majority of patients but there are still instances of acute failure most often due to anatomical differences, for example due to tortuous CS anatomy. Chronic LV lead misplacement and its delayed discovery is not a common scenario. It is unclear if chronic dual right ventricular pacing can hasten the progression of heart failure. Case presentation: A 73-year-old lady presented to our cardiac centre with severe heart failure. She had non-ischaemic dilated cardiomyopathy with underlying left bundle branch block and a cardiac resynchronization therapy-defibrillator device in situ for the past decade. She also had a chronic pericardial effusion of unknown aetiology. Whilst the patient was being treated for acute heart failure, it was noted on patient telemetry that the QRS morphology for supposed bi-ventricular pacing was unusual. This led to a lateral chest radiograph and a CS venogram to be performed, both of which confirmed that the LV lead was in fact not in the CS. Plans were made to place a new LV lead but unfortunately the patient continued to clinically deteriorate despite maximal treatment and died before this could be performed. Discussion: It is only with thorough review of the electrocardiographic data and chest radiography that led to the discovery of chronic LV lead misplacement. This case illustrates the importance of expert review of radiographic imaging and electrocardiographic data in patients with implanted cardiac devices

Remanufactured circular mapping catheters: safety, effectiveness and cost.

BACKGROUND: The use of remanufactured single-use devices (SUDs), including cardiac electrophysiology catheters, has become established in the USA and other health care systems but without much published scientific evaluation on the relative safety or efficacy of these devices. In the United Kingdom (UK), the use of remanufactured SUDs has not been routine. We performed a structured evaluation of the safety and efficacy of a remanufactured circular mapping catheter (Stryker® remanufactured Lasso NAV 2515) during its introduction in our centre. METHODS: We prospectively evaluated the performance of a remanufactured circular mapping catheter in 100 consecutive patients undergoing an AF ablation. Operator feedback was obtained, assessing the device appearance, ease of use and function. As an indirect measurement of efficacy, acute procedure metrics were compared to those in 100 propensity-matched cases performed by the same operators using a new device. Cost savings were calculated. RESULTS: No complication occurred in association with the remanufactured device. There was one reported failure of device malfunction-the flexion-extension mechanism of a remanufactured catheter and none in the matched-control group. There was satisfactory communication with the electro-anatomic mapping system. Ease of use of the remanufactured catheter was reported to be similar to a newly manufactured device. Procedural duration was similar with remanufactured devices and matched controls. With 100 cases using the remanufactured device, cost savings amounted to £30,444. CONCLUSIONS: The use of remanufactured circular mapping catheters is safe, efficient and reliable. Widespread use of remanufactured SUDs offers the possibility of significant economic benefit

Multi-catheter cryotherapy for the treatment of resistant accessory pathways.

OBJECTIVE: To investigate the utility of simultaneous multi-catheter cryotherapy for the treatment of APs that were previously resistant to standard radiofrequency (RF) catheter ablation. BACKGROUND: Catheter ablation is established in the treatment of accessory pathways (AP), with high rates of permanent procedural success with a single attempt. However, there are still instances of acute procedural failure and AP recurrences with standard RF and cryotherapy methods. METHODS: Seven consecutive cases of pre-excitation syndromes with prior failed RF catheter ablation had the novel treatment. Cryotherapy was delivered using two 8 mm tip focal cryoablation catheters (Freezor® Max, Medtronic, Minneapolis, Minnesota, USA). RESULTS: Accessory pathway localisation was septal in 5 cases, left posterolateral in 1, right lateral in 1. In all cases, ablation of the AP was acutely successful with no procedural complications. Median procedure and fluoroscopy durations were 199 and 35 min, sequentially. Median Procedure duration fell significantly in the second half of series (174 min) compared to the first half (233 min, P = 0.05). One patient had evidence of a recurring AP conduction with pre-excitation at 5-week follow up. After a median follow up of 66.8+-6.5 months, 6 out of 7 patients remained asymptomatic and free of pre-excitation. CONCLUSION: Simultaneous multi-catheter cryotherapy is feasible, safe and can provide definitive cure of accessory pathways that were previously resistant to standard radiofrequency ablation. Further study is required in the assessment of this novel form of advanced cryotherapy to treat complex and resistant arrhythmias

Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D1-R/D2-R/5-HT2A -R/H3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs

Investigation of Synthesis, Molecular Modelling and Monoaminoxidase Inhibitor Activity of a New 2-Pyrazoline Compound

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Case Image: Occurrence of Atrial Fibrillation While Isolating The Left Atrial Appendage Due To Vasospasm At The Sinoatrial Node Artery

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