The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade.

尽管 β-阻滞,心脏交感神经共递质神经肽 Y 在 ST 段抬高型心肌梗死后是促心律失常。

  • 影响因子:8.07
  • DOI:10.1093/eurheartj/ehz852
  • 作者列表:"Kalla M","Hao G","Tapoulal N","Tomek J","Liu K","Woodward L","‘Oxford Acute Myocardial Infarction (OxAMI) Study’.","Dall'Armellina E","Banning AP","Choudhury RP","Neubauer S","Kharbanda RK","Channon KM","Ajijola OA","Shivkumar K","Paterson DJ","Herring N
  • 发表时间:2020-06-14

AIMS:ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors. METHODS AND RESULTS:In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P < 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304. CONCLUSIONS:The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy.


目的: ST 段抬高型心肌梗死与高水平的心脏交感神经驱动和共递质神经肽 Y (NPY) 的释放有关。我们假设尽管有 β-阻滞,NPY 通过心室肌细胞受体促进心律失常发生。 方法和结果: 78 例直接经皮冠状动脉介入治疗患者中,6 例 (7.7%) 在 48 h 内发生持续性室性心动过速 (VT) 或室颤 (VF)。这些患者静脉 NPY 水平显著 (p <0.05) 较高,尽管没有经典的危险因素,包括晚期表现、较大的梗死面积和 β 受体阻滞剂的使用。受试者工作曲线确定 NPY 阈值为 27.3 pg/mL,敏感性为 0.83,特异性为 0.71。RT-qPCR 证明 NPY mRNA 在人和大鼠星状神经节中都存在。在离体 Langendorff 灌注大鼠心脏中,持续 (10 hz,2 min) 刺激星状神经节引起显著的 NPY 释放。尽管美托洛尔 (10 μ mol/L) 最大限度地阻断 β-,心室电压和钙的光学标测 (使用 RH237 和 Rhod2) 证明钙瞬变的幅度增加和持续时间缩短,心室颤动阈值显著降低。Y1 受体拮抗剂 BIBO3304 (1 μ mol/L) 可阻止这些作用。神经肽 Y (250 nmol/L) 显著增加 VT/VF 的发生率 (60% vs. 10%) 与对照组相比,在实验性 ST 段抬高缺血和再灌注期间,这也可以通过 bibo3304 来预防。 结论: 共递质 NPY 在交感神经刺激过程中释放,作为一种新的心律失常触发因子。抑制 Y1 受体工作的药物与 β-阻滞协同作为一种新的抗心律失常治疗。



作者列表:["Berte B","Hilfiker G","Moccetti F","Schefer T","Weberndörfer V","Cuculi F","Toggweiler S","Ruschitzka F","Kobza R"]

METHODS:AIMS:Pulmonary vein isolation (PVI) using ablation index (AI) incorporates stability, contact force (CF), time, and power. The CLOSE protocol combines AI and ≤6 mm interlesion distance. Safety concerns are raised about surround flow ablation catheters (STSF). To compare safety and effectiveness of an atrial fibrillation (AF) ablation strategy using AI vs. CLOSE protocol using STSF.,METHODS AND RESULTS:First cluster was treated using AI and second cluster using CLOSE. Procedural data, safety, and recurrence of any atrial tachycardia (AT) or AF >30 s were collected prospectively. All Classes 1c and III anti-arrhythmic drugs (AAD) were stopped after the blanking period. In total, all 215 consecutive patients [AI: 121 (paroxysmal: n = 97), CLOSE: n = 94 (paroxysmal: n = 74)] were included. Pulmonary vein isolation was reached in all in similar procedure duration (CLOSE: 107 ± 25 vs. AI: 102 ± 24 min; P = 0.1) and similar radiofrequency time (CLOSE: 36 ± 11 vs. AI: 37 ± 8 min; P = 0.4) but first pass isolation was higher in CLOSE vs. AI [left veins: 90% vs. 80%; P < 0.05 and right veins: 84% vs. 73%; P < 0.05]. Twelve-month off-AAD freedom of AF/AT was higher in CLOSE vs. AI [79% (paroxysmal: 85%) vs. 64% (paroxysmal: 68%); P < 0.05]. Only four patients (2%) without recurrence were on AAD during follow-up. Major complications were similar (CLOSE: 2.1% vs. AI: 2.5%; P = 0.87).,CONCLUSION:The CLOSE protocol is more effective than a PVI approach solely using AI, especially in paroxysmal AF. In this off-AAD study, 79% of patients were free from AF/AT during 12-month follow-up. The STSF catheter appears to be safe using conventional CLOSE targets.

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作者列表:["Qin M","Jiang WF","Wu SH","Xu K","Liu X"]

METHODS:OBJECTIVE:To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression.,METHODS:A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping.,RESULTS:The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001).,CONCLUSION:The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.

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作者列表:["Takamiya T","Nitta J","Inaba O","Sato A","Ikenouchi T","Murata K","Inamura Y","Takahashi Y","Goya M","Hirao K"]

METHODS:PURPOSE:Whether or not pulmonary vein isolation (PVI) plus left atrial posterior wall isolation (PWI) using contact force (CF) sensing improves the ablation outcome for persistent atrial fibrillation (AF) is unclear. This study compared the outcome of PVI plus PWI and additional non-PV trigger ablation for persistent AF with/without CF sensing. METHODS:This retrospective cohort study analyzed 148 propensity score-matched persistent AF patients (median duration of persistent AF, 8 months (interquartile range, 3-24 months); left atrial diameter, 43 ± 7 mm) undergoing PVI plus PWI and ablation of non-PV triggers provoked by high-dose isoproterenol, including 74 with CF-sensing catheters (CF group) and 74 with conventional catheters (non-CF group). PVI plus PWI with no additional ablation but cavotricuspid isthmus ablation was performed without non-PV triggers in 48 CF patients (65%) and 54 non-CF patients (73%) (P = 0.38). In all other patients, we performed additional ablation of provoked non-PV triggers. RESULTS:The Kaplan-Meier estimate of the rate of freedom from atrial tachyarrhythmia recurrence of antiarrhythmic drugs at 12 months after the single procedure was higher in the CF group than in the non-CF group (85 vs. 70%, log-rank P = 0.030). A multivariable analysis revealed that using CF sensing and non-inducibility of AF from a non-PV trigger after PVI and PWI were significantly associated with a reduced rate of atrial tachyarrhythmia recurrence. CONCLUSIONS:Compared with non-CF sensing, PVI plus PWI and additional non-PV trigger ablation using CF-sensing catheters for persistent AF can reduce the rate of atrial tachyarrhythmia recurrence.

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