Bierhuizen Mark F A, Amesz Jorik H, Langmuur Sanne J J, Lam Bobby, Knops Paul, Veen Kevin M, Manintveld Olivier C, Kluin Jolanda, de Groot Natasja M S, Taverne Yannick J H J
Department of Cardiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Translational Cardiothoracic Surgery Research Lab, Department of Cardiothoracic Surgery Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Bioengineering (Basel). 2025 Feb 12;12(2):174. doi: 10.3390/bioengineering12020174.
Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587-2658) vs. baseline: 1066 µN (529-2128), = 0.05) and area under the contractile curve (CCM: 297 (151-562) vs. baseline: 243 (129-464), = 0.05) but did not significantly impact contractile duration, time to peak, or time to relaxation. Increasing CCM stimulation delay, duration, and amplitude resulted in a higher fraction of LMS with a positive inotropic response. Furthermore, CCM attenuated the negative force-frequency relationship in HF-LMS. CCM stimulation enhanced contractile force in HF-LMS. The fraction of LMS exerting a positive inotropic response to CCM increased with increasing delay, duration, and amplitude settings, suggesting that personalizing stimulation parameters could optimize the beneficial effects of CCM. CCM is a novel device-based therapy that may improve contractile function, ejection fraction, functional outcomes, and quality of life in patients with heart failure. However, continuous efforts are needed to identify true responders to CCM therapy, understand the exact mechanisms, and optimize the contractile response to CCM stimulation. The present study revealed that CCM enhanced the contractile force of HF-LMS in a stimulation setting-dependent manner, reaching a larger fraction of the myocardium while increasing delay, duration, and amplitude. This understanding may contribute to the individualization of CCM stimulation settings.
用于确定心脏收缩力调制（CCM）对终末期心力衰竭（HF）患者的活体心肌切片（LMS）直接生物力学效应的概念验证。制备了终末期HF患者的左心室LMS，并在具有机械负荷和电刺激的仿生系统中进行培养。CCM刺激（80 mA，延迟40 ms，持续时间21 ms）增强了最大收缩力（CCM：1229 μN（587 - 2658）vs. 基线：1066 μN（529 - 2128），P = 0.05）和收缩曲线下面积（CCM：297（151 - 562）vs. 基线：243（129 - 464），P = 0.05），但对收缩持续时间、达到峰值时间或松弛时间没有显著影响。增加CCM刺激的延迟、持续时间和幅度会导致具有正性肌力反应的LMS比例更高。此外，CCM减弱了HF-LMS中负性的力-频率关系。CCM刺激增强了HF-LMS的收缩力。对CCM产生正性肌力反应的LMS比例随着延迟、持续时间和幅度设置的增加而增加，这表明个性化刺激参数可以优化CCM的有益效果。CCM是一种基于装置的新型疗法，可能改善心力衰竭患者的收缩功能、射血分数、功能结局和生活质量。然而，需要持续努力来识别CCM治疗的真正反应者，了解确切机制，并优化对CCM刺激的收缩反应。本研究表明，CCM以刺激设置依赖的方式增强了HF-LMS的收缩力，在增加延迟、持续时间和幅度的同时，使更大比例的心肌受到影响。这种认识可能有助于CCM刺激设置的个体化。
