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临床试验/NCT03727542
NCT03727542已完成不适用

Influence of Short AV Delay Pacing on Matrix Metalloproteinase Lives

Istanbul University2 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2018年10月15日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
已完成
入组人数
20
试验地点
2
主要终点
Change in MMP - 9 serum concentration from baseline to at the end of 3 weeks follow-up

研究概览

简要总结

As potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they play in connective tissue homeostasis. In particular, a significant reduction in initially elevated serum MMP - 9 concentrations, compared with healthy controls, demonstrated after the aortic repair in patients with abdominal aortic aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation and repair processes taking place in the vascular wall governed by the balance between MMP enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects. Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP expression in the vascular wall, which is responsible for extracellular matrix degradation. Herein, it was hypothesized that reducing the acceleration rate of aortic pressure (aortic peak dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the expression and serum levels of MMP-9.

详细描述

The maximum value of acceleration rate of aortic pressure rise can be named as aortic peak dP/dt. It, likewise, corresponds to the maximum value of first derivative of aortic pressure curve with respect to time.Notably, aortic peak dP/dt would be one of the principal determinants of mechanical stress applied to the aortic wall. Hence, interventions aiming to reduce aortic peak dP/dt levels may open a new therapeutic avenue in the management of pressure-related vascular damages such as aortic aneurisms.

Since it is the principle determining factor of aortic peak dP/dt, changing LV contractility, thereby LV peak dP/dt, may be expected to lead to change aortic peak dP/dt values in the same direction. Therefore, reduction of LV dP/dt can lead to a reduction in aortic dP/dt. Previous finding strongly suggest that widening of the QRS complex could decrease LV contractility and correspondingly LV peak dP/dt value which may eventually lead to a reduction in aortic peak dP/dt.

From biomechanical point of view, as potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they play in connective tissue homeostasis. In particular, a significant reduction in initially elevated serum MMP - 9 concentrations, compared with healthy controls, demonstrated after the aortic repair in patients with abdominal aortic aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation and repair processes taking place in the vascular wall governed by the balance between MMP enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects. Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP expression in the vascular wall, which is responsible for extracellular matrix degradation. Herein, we hypothesized that reducing the acceleration rate of aortic pressure (aortic peak dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the expression and serum levels of MMP-9.

To this end, in the current trial, effect of the prolongation of QRS duration over a certain period of time by short AVD permanent pacing on the circulating levels of a vascular extracellular matrix degradation marker, MMP-9, was examined.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Diagnostic
盲法
None

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Normal LV systolic function (EF>50%),
  • Healthy conduction systems
  • Noncritical coronary stenoses or normal coronary arteries
  • Ventricular pacing rate <10% in the last 6 months detected at the interrogation of the pacemakers

排除标准

  • Intra-ventricular conduction abnormalities (baseline QRS >100 msec.),
  • Mild to moderate aortic or mitral valve disease
  • Presence of atrial fibrillation
  • LV systolic dysfunction

研究组 & 干预措施

Short AV-delay pacing

Experimental

Participants will be their own control. Serum samples will be collected at baseline while the participants were in sinus rhythm and after 3 weeks of short AV-delay pacing serum samples will be recollected to measure matrix metalloproteinase levels .

干预措施: adjustment of atrioventricular delay in DDD packers (Device)

结局指标

主要结局

Change in MMP - 9 serum concentration from baseline to at the end of 3 weeks follow-up

时间窗: 3 weeks

MMP-9 serum concentration will be measured before and after short AV delay (wide QRS) pacing. Change in MMP-9 levels will be measured.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dr. Murat Sezer

Clinical Professor

Istanbul University

研究点 (2)

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