BSICoS Group, I3A, University of Zaragoza, Zaragoza, Spain.
IIS Aragón, Zaragoza, Spain.
PLoS One. 2023 Jan 26;18(1):e0280901. doi: 10.1371/journal.pone.0280901. eCollection 2023.
The adaptation lag of the QT interval after heart rate (HR) has been proposed as an arrhythmic risk marker. Most studies have quantified the QT adaptation lag in response to abrupt, step-like changes in HR induced by atrial pacing, in response to tilt test or during ambulatory recordings. Recent studies have introduced novel methods to quantify the QT adaptation lag to gradual, ramp-like HR changes in stress tests by evaluating the differences between the measured QT series and an estimated, memoryless QT series obtained from the instantaneous HR. These studies have observed the QT adaptation lag to progressively reduce when approaching the stress peak, with the underlying mechanisms being still unclear. This study analyzes the contribution of β-adrenergic stimulation to QT interval rate adaptation in response to gradual, ramp-like HR changes. We first quantify the QT adaptation lag in Coronary Artery Disease (CAD) patients undergoing stress test. To uncover the involved mechanisms, we use biophysically detailed computational models coupling descriptions of human ventricular electrophysiology and β-adrenergic signaling, from which we simulate ventricular action potentials and ECG signals. We characterize the adaptation of the simulated QT interval in response to the HR time series measured from each of the analyzed CAD patients. We show that, when the simulated ventricular tissue is subjected to a time-varying β-adrenergic stimulation pattern, with higher stimulation levels close to the stress peak, the simulated QT interval presents adaptation lags during exercise that are more similar to those measured from the patients than when subjected to constant β-adrenergic stimulation. During stress test recovery, constant and time-varying β-adrenergic stimulation patterns render similar adaptation lags, which are generally shorter than during exercise, in agreement with results from the patients. In conclusion, our findings support the role of time-varying β-adrenergic stimulation in contributing to QT interval adaptation to gradually increasing HR changes as those seen during the exercise phase of a stress test.
QT 间期(QT interval)随心率(HR)的适应性滞后已被提出作为心律失常风险标志物。大多数研究通过心房起搏、倾斜试验或动态记录,来量化 HR 突然、阶跃式变化引起的 QT 适应性滞后。最近的研究提出了新的方法,通过评估测量的 QT 序列与从即时 HR 获得的无记忆 QT 序列之间的差异,来量化应激试验中 QT 适应性滞后与逐渐、斜坡式 HR 变化之间的关系。这些研究观察到随着接近应激峰值,QT 适应性滞后逐渐减小,但其潜在机制尚不清楚。本研究分析了β-肾上腺素能刺激对 QT 间期率适应的贡献,以应对逐渐、斜坡式 HR 变化。我们首先在进行应激试验的冠心病(CAD)患者中量化 QT 适应性滞后。为了揭示涉及的机制,我们使用耦合人类心室电生理学和β-肾上腺素能信号描述的详细生物物理计算模型,从该模型中模拟心室动作电位和 ECG 信号。我们对模拟 QT 间期在响应从每位分析的 CAD 患者测量的 HR 时间序列的适应进行了特征描述。我们表明,当模拟心室组织受到时变β-肾上腺素能刺激模式的作用,在接近应激峰值的位置具有更高的刺激水平时,模拟 QT 间期在运动期间表现出的适应性滞后与从患者测量的更为相似,而不是在受到恒常β-肾上腺素能刺激时。在应激试验恢复期间,恒常和时变β-肾上腺素能刺激模式产生的适应性滞后相似,与患者的结果一致,这些滞后通常比运动期间更短。总之,我们的研究结果支持了时变β-肾上腺素能刺激在贡献 QT 间期适应逐渐增加的 HR 变化方面的作用,这种变化类似于应激试验运动阶段所见的变化。