Choy Jenny S, Fan Lei, Awakeem Yousif, Cai Chenghan, Raissi Farshad, Lee Lik Chuan, Kassab Ghassan S
California Medical Innovations Institute, Inc., San Diego, CA, United States.
Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.
Front Bioeng Biotechnol. 2025 Sep 12;13:1630854. doi: 10.3389/fbioe.2025.1630854. eCollection 2025.
Patients with heart failure frequently develop mechanical dyssynchrony, which impairs ventricular function, coronary perfusion and their interactions. The underlying mechanisms, however, remain poorly understood due to numerous confounding factors. The objective of this study was to determine the acute effects of mechanical dyssynchrony on global and regional left ventricular (LV) function, coronary perfusion and their interactions based on experimental and computational approaches.
Mechanical dyssynchrony was created with right ventricular apical pacing in Yorkshire domestic swine (n = 9). The heart was paced at 100 and 140 bpm and the results were compared to right atrial pacing. An inverse finite element computational framework based on an animal-specific geometry of the LV and measurements was developed to investigate the effects of mechanical dyssynchrony on LV function and its correlation with regional coronary perfusion.
Cardiac dyssynchrony induced significant decrease in LV pressure, volume, dP/dt, stroke volume, ejection fraction, and regional longitudinal and circumferential strain. With mechanical dyssynchrony, passive flow decreased by 70% in the left anterior descending artery (LAD) and 67% in the left circumflex (LCX). An animal-specific inverse finite element computational model predicted that in mechanical dyssynchrony, global and regional LV contractility in the septum and LV free wall (LVFW), and myocardial work done in the septum and LVFW decreased.
The computational model predicted reduction in global and regional contractility, and regional myocardial work done in the septum and LVFW with mechanical dyssynchrony are positively correlated with the corresponding decrease in experimentally measured regulated coronary flow in the LAD and LCX. These findings demonstrate that this interrelated mechanism between LV function and coronary flow in mechanical dyssynchrony may affect cardiac resynchronization therapy responder rate.
心力衰竭患者常出现机械性不同步，这会损害心室功能、冠状动脉灌注及其相互作用。然而，由于众多混杂因素，其潜在机制仍知之甚少。本研究的目的是基于实验和计算方法，确定机械性不同步对整体和局部左心室（LV）功能、冠状动脉灌注及其相互作用的急性影响。
在约克夏家猪（n = 9）中通过右心室心尖起搏产生机械性不同步。以100和140次/分钟的频率进行心脏起搏，并将结果与右心房起搏进行比较。基于LV的动物特异性几何形状和测量结果，开发了一个反向有限元计算框架，以研究机械性不同步对LV功能的影响及其与局部冠状动脉灌注的相关性。
心脏不同步导致LV压力、容积、dP/dt、每搏量、射血分数以及局部纵向和周向应变显著降低。出现机械性不同步时，左前降支（LAD）的被动血流减少70%，左旋支（LCX）减少67%。一个动物特异性反向有限元计算模型预测，在机械性不同步时，室间隔和左心室游离壁（LVFW）的整体和局部LV收缩性以及室间隔和LVFW所做的心肌功会降低。
计算模型预测，机械性不同步时整体和局部收缩性以及室间隔和LVFW所做的局部心肌功降低，与实验测量的LAD和LCX中调节冠状动脉血流的相应减少呈正相关。这些发现表明，机械性不同步中LV功能和冠状动脉血流之间的这种相互关联机制可能会影响心脏再同步治疗的反应率。
