Persistent Proarrhythmic Neural Remodeling Despite Recovery From Premature Ventricular Contraction-Induced Cardiomyopathy.


  • 影响因子:6.43
  • DOI:10.1016/j.jacc.2019.10.046
  • 作者列表:"Tan AY","Elharrif K","Cardona-Guarache R","Mankad P","Ayers O","Joslyn M","Das A","Kaszala K","Lin SF","Ellenbogen KA","Minisi AJ","Huizar JF
  • 发表时间:2020-01-07

BACKGROUND:The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVES:This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM. METHODS:In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls. RESULTS:After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls. CONCLUSIONS:Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.


背景: 室性期前收缩诱导的心肌病 (pvc-二1212) 中神经重构的存在和意义仍然未知。 目的: 本研究旨在描述犬PVC二1212模型的心脏交感迷走神经平衡和心律失常。 方法: 在12只犬中,研究人员植入心外膜起搏器和无线电遥测装置,记录左星状神经节 (SNA) 、左心迷走神经 (VNA) 和动脉血压的心律和神经活动。与5个假对照相比,在7只动物中应用双嵌合PVCs (200 ms偶联) 12周以诱导pvc-二1212,然后禁用4周以允许左心室射血分数 (LVEF) 的完全恢复。 成果: PVCs术后12周,LVEF (p = 0.006) 和dP/dT (p = 0.007) 降低。静息SNA (p = 0.002) 和VNA (p = 0.04) 、运动SNA (p = 0.01) 、SNA对诱发PVCs的反应 (p = 0.005) 、静息时心率 (HR) (p = 0.003) 和运动 (p < 0.04) 增加,而心率变异性 (HRV) 降低(p = 0.009)。PVC二1212组自发性心房 (p = 0.02) 和室性心律失常 (p = 0.03) 增加。SNA增加先于心房 (p = 0.0003) 和心室 (p = 0.009) 心律失常发作。可乐定抑制SNA并消除所有心律失常。禁用PVC 4周后,LVEF (p = 0.01) 、dP/dT (p = 0.047) 和静息VNA (p = 0.03) 恢复至基线水平。然而,SNA、静息心率、HRV和心房 (p = 0.03) 和心室 (p = 0.03) 前心律失常持续存在。与假对照相比,pvc-二1212和康复动物的星状神经节 (p = 0.02) 中存在交感神经过度支配,但心室中不存在 (p = 0.2)。 结论: PVC二1212的神经重塑以心外交感神经过度支配和交感神经过度活跃为特征,尽管LVEF正常化,但仍持续存在。改变的心脏交感迷走神经平衡是心房和室性心律失常的重要触发和底物。



作者列表:["Yaghi S","Chang AD","Akiki R","Collins S","Novack T","Hemendinger M","Schomer A","Grory BM","Cutting S","Burton T","Song C","Poppas A","McTaggart R","Jayaraman M","Merkler A","Kamel H","Elkind MSV","Furie K","Atalay MK"]

METHODS:BACKGROUND AND PURPOSE:The current left atrial appendage (LAA) classification system (cLAA-CS) categorizes it into 4 morphologies: chicken wing (CW), windsock, cactus, and cauliflower, though there is limited data on either reliability or associations between different morphologies and stroke risk. We aimed to develop a simplified LAA classification system and to determine its relationship to embolic stroke subtypes. METHODS:Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology was classified using the traditional system (in which CW = low risk) and a new system (LAA-H/L, in which low risk morphology (LAA-L) was defined as an acute angle bend or fold from the proximal/middle portion of the LAA and high risk morphology (LAA-H) was defined as all others). As a proof of concept study, we determined reliability for the two classification systems, and we assessed the associations between both classification systems with stroke subtypes in our cohort and previous studies. RESULTS:We identified 329 ischemic stroke patients with a qualifying chest CT (126 cardioembolic subtype, 116 embolic stroke of undetermined source (ESUS), and 87 non-cardioembolic subtypes). Intra- and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85, respectively) vs. cLAA-CS (0.50 and 0.40). The LAA-H/L led to classifying 69 LAA morphologies that met criteria for CW as LAA-H. In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter- and intra-rater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes. CONCLUSION:The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk identify patients with cardioembolic stroke subtypes. Larger studies are needed to validate these findings.

作者列表:["Kim S","Namba J","Goodman AM","Nguyen T","Saunders IM"]

METHODS:PURPOSE:Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. METHODS:This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. RESULTS:A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. CONCLUSION:Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

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作者列表:["Harky A","Chaplin G","Chan JSK","Eriksen P","MacCarthy-Ofosu B","Theologou T","Muir AD"]

METHODS::It has been over two decades since the very first robotic cardiac surgery was performed. Over the years, there has been an increase in the demand for less invasive cardiac surgical techniques. Developments in technology and engineering have provided an opportunity for robotic surgery to be applied to a variety of cardiac procedures, including coronary revascularisation, mitral valve surgery, atrial fibrillation ablation, and others. In coronary revascularisation, it is becoming more widely used in single vessel, as well as hybrid coronary artery approaches. Currently, several international centres are specialising in a totally endoscopic coronary artery bypass surgery involving multiple vessels. Mitral valve and other intracardiac pathologies such as atrial septal defect and intracardiac tumour are also increasingly being addressed robotically. Even though some studies have shown good results with robot-assisted cardiac surgery, there are still concerns about safety, cost and clinical efficacy. There are also limitations and additional challenges with the management of cardiopulmonary bypass and myocardial protection during robotic surgery. Implementing novel strategies to manage these challenges, together with careful patient selection can go a long way to producing satisfactory results. This review examines the current evidence behind robotic surgery in various aspects of cardiac surgery.

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