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-cm) 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-CM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-cm,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-CM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-cm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-CM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:["Cui H","Schaff HV","Abel MD","Helder MRK","Frye RL","Ommen SR","Nishimura RA"]

METHODS:OBJECTIVE:There has been debate on the importance and pathophysiologic effects of the dynamic subaortic pressure gradient in hypertrophic obstructive cardiomyopathy. The study was conducted to elucidate the hemodynamic abnormalities associated with the dynamic pressure gradient in hypertrophic obstructive cardiomyopathy. METHODS:Eight patients with hypertrophic obstructive cardiomyopathy and 7 patients with valvular aortic stenosis underwent a detailed hemodynamic study of pressure flow relationships before and after myectomy or aortic valve replacement during operation. RESULTS:In aortic stenosis, the increased gradient after premature ventricular contraction was associated with an increase in peak flow (325 ± 122 mL/s to 428 ± 147 mL/s, P = .002) and stroke volume (75.0 ± 27.3 mL to 88.0 ± 24.0 mL, P = .004), but in hypertrophic obstructive cardiomyopathy peak flow remained unchanged (289 ± 79 mL/s to 299 ± 85 mL/s, P = .334) and stroke volume decreased (45.9 ± 18.7 mL to 38.4 ± 14.4 mL, P = .04) on the postpremature ventricular contraction beat. After myectomy, the capacity to augment stroke volume on the postpremature ventricular contraction beats was restored in patients with hypertrophic obstructive cardiomyopathy (45.6 ± 14.4 mL to 54.4 ± 11.8 mL, P = .002). CONCLUSIONS:The pressure flow relationship in hypertrophic obstructive cardiomyopathy supports the concept of true obstruction to outflow, with a low but continued flow during late systole, when the ventricular-aortic pressure gradient is the highest. Septal myectomy can abolish obstruction and restore the ability to augment stroke volume, which may explain the mechanism of symptomatic improvement after operation.

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作者列表:["Gülsaran SK","Baysal M","Demirci U","Baş V","Kirkizlar HO","Umit E","Demir AM"]

METHODS:INTRODUCTION:Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, has altered the treatment perspective of chronic lymphocytic leukemia and showed modest activity against several types of non-Hodgkin's lymphomas. According to phase studies and real-world data, reported serious adverse effects included atrial fibrillation, diarrhea, and bleeding diathesis. However, heart failure was not reported to be a probable adverse effect linked with ibrutinib. CASE REPORT:In this paper, we present a 66-year-old female chronic lymphocytic leukemia patient who developed significant and symptomatic left ventricular dysfunction at the 13th month of ibrutinib treatment. MANAGEMENT AND OUTCOME:Following cessation of ibrutinib, ejection fraction and clinical findings of the left ventricular dysfunction alleviated. DISCUSSION:Although the use of ibrutinib is generally well tolerated, cardiac functions should be monitored occasionally in all patients.

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作者列表:["Ishigaki T","Shingu Y","Katoh N","Wakasa S","Katoh H","Ooka T","Kubota S","Matsui Y"]

METHODS:OBJECTIVES:The slope in the preload recruitable stroke work relationship is a highly linear, load-insensitive contractile parameter. However, the perioperative change of the slope has not been reported before. We examined the perioperative slope from a steady-state single beat in patients with functional mitral regurgitation and assessed the correlation with brain natriuretic peptide (BNP) levels. METHODS:The study included 16 patients with non-ischemic dilated cardiomyopathy and refractory heart failure: 10 patients underwent mitral valve plasty and left ventricular plasty (MVP + LVP group) and 6 patients who underwent mitral valve replacement and papillary muscle tugging approximation (MVR + PMTA group). The left ventricular ejection fraction was assessed by the modified Simpson method; the slope was assessed by the single-beat technique using transthoracic echocardiography. BNP levels were measured by chemiluminescent immunoassay. RESULTS:The left ventricular ejection fraction and slope did not significantly change from pre- to early post-surgery in the MVP + LVP group. Both the left ventricular ejection fraction and slope significantly increased 6 months after surgery in the MVR + PMTA group. Postoperative BNP level was low in the MVR + PMTA group. While the postoperative left ventricular ejection fraction did not correlate with BNP levels, the postoperative slope significantly correlated with BNP level after surgery in the MVP + LVP group and in the total functional mitral regurgitation group. CONCLUSIONS:The change of slope was dependent on surgical procedures. In functional mitral regurgitation, the slope may be a more sensitive parameter in reflecting the left ventricular contractile function than the left ventricular ejection fraction.

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