Dabiri Yaghoub, Sack Kevin L, Shaul Semion, Sengupta Partho P, Guccione Julius M
Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
Section of Cardiology, West Virginia University Heart and Vascular Institute, West Virginia University, Morgantown, WV, United States.
Front Physiol. 2018 Aug 24;9:1003. doi: 10.3389/fphys.2018.01003. eCollection 2018.
The pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocardial dysfunction and compensatory increased subepicardial contractility may underlie preservation of LVEF in patients with HFpEF. We quantified alterations in myocardial function in a mathematical model of the human LV that is based on the finite element method. The fiber-reinforced material formulation of the myocardium included passive and active properties. The passive material properties were determined such that the diastolic pressure-volume behavior of the LV was similar to that shown in published clinical studies of pressure-volume curves. To examine changes in active properties, we considered six scenarios: (1) normal properties throughout the LV wall; (2) decreased myocardial contractility in the subendocardium; (3) increased myocardial contractility in the subepicardium; (4) myocardial contractility decreased equally in all layers, (5) myocardial contractility decreased in the midmyocardium and subepicardium, (6) myocardial contractility decreased in the subepicardium. Our results indicate that decreased subendocardial contractility reduced LVEF from 53.2 to 40.5%. Increased contractility in the subepicardium recovered LVEF from 40.5 to 53.2%. Decreased contractility transmurally reduced LVEF and could not be recovered if subepicardial and midmyocardial contractility remained depressed. The computational results simulating the effects of transmural alterations in the ventricular tissue replicate the phenotypic patterns of LV dysfunction observed in clinical practice. In particular, data for LVEF, strain and displacement are consistent with previous clinical observations in patients with HFpEF, and substantiate the hypothesis that increased subepicardial contractility may compensate for subendocardial dysfunction and play a vital role in maintaining LVEF.
射血分数保留的心力衰竭（HFpEF）患者左心室（LV）射血分数（EF）得以保留的病理生理机制仍未完全明了。我们推测，心肌纤维收缩性的透壁差异以及心内膜下功能障碍的存在和心外膜下收缩性的代偿性增加，可能是HFpEF患者LVEF得以保留的基础。我们在基于有限元法的人体左心室数学模型中对心肌功能的改变进行了量化。心肌的纤维增强材料公式包含被动和主动特性。确定被动材料特性，以使左心室的舒张压力-容积行为与已发表的压力-容积曲线临床研究中所示的行为相似。为了研究主动特性的变化，我们考虑了六种情况：（1）整个左心室壁特性正常；（2）心内膜下心肌收缩性降低；（3）心外膜下心肌收缩性增加；（4）所有层心肌收缩性均同等降低；（5）心肌中层和心外膜下心肌收缩性降低；（6）心外膜下心肌收缩性降低。我们的结果表明，心内膜下收缩性降低使LVEF从53.2%降至40.5%。心外膜下收缩性增加使LVEF从40.5%恢复至53.2%。透壁性收缩性降低使LVEF降低，并且如果心外膜下和心肌中层收缩性仍然降低则无法恢复。模拟心室组织透壁改变影响的计算结果复制了临床实践中观察到的左心室功能障碍的表型模式。特别是，LVEF、应变和位移的数据与HFpEF患者先前的临床观察结果一致，并证实了心外膜下收缩性增加可能补偿心内膜下功能障碍并在维持LVEF中起重要作用这一假说。
