The highly organized transverse T-tubule membrane system represents the ultrastructural substrate for excitation–contraction coupling in ventricular myocytes. While the architecture and function of T-tubules have been well described in animal models, there is limited morpho-functional data on T-tubules in human myocardium. Hypertrophic cardiomyopathy (HCM) is a primary disease of the heart muscle, characterized by different clinical presentations at the various stages of its progression. Most HCM patients, indeed, show a compensated hypertrophic disease (“non-failing hypertrophic phase”), with preserved left ventricular function, and only a small subset of individuals evolves into heart failure (“end stage HCM”). In terms of T-tubule remodeling, the “end-stage” disease does not differ from other forms of heart failure. In this review we aim to recapitulate the main structural features of T-tubules during the “non-failing hypertrophic stage” of human HCM by revisiting data obtained from human myectomy samples. Moreover, by comparing pathological changes observed in myectomy samples with those introduced by acute (experimentally induced) detubulation, we discuss the role of T-tubular disruption as a part of the complex excitation–contraction coupling remodeling process that occurs during disease progression. Lastly, we highlight how T-tubule morpho-functional changes may be related to patient genotype and we discuss the possibility of a primitive remodeling of the T-tubule system in rare HCM forms associated with genes coding for proteins implicated in T-tubule structural integrity, formation and maintenance.

高度组织化的横向 T 小管膜系统代表了心室肌细胞中兴奋-收缩耦合的超微结构底物。虽然 T 小管的结构和功能已在动物模型中得到很好的描述，但人类心肌中 T 小管的形态功能数据有限。肥厚型心肌病 (HCM) 是心肌的一种原发性疾病，其特点是在其进展的不同阶段有不同的临床表现。事实上，大多数 HCM 患者表现出代偿性肥大疾病（“非衰竭性肥大期”），左心室功能保留，只有一小部分个体发展为心力衰竭（“终末期 HCM”）。在 T 小管重塑方面，“终末期”疾病与其他形式的心力衰竭没有区别。在这篇综述中，我们旨在通过重新审视从人类肌切除术样本中获得的数据，概括 T 小管在人类 HCM 的“非失败肥大阶段”期间的主要结构特征。此外，通过比较在肌切除术样本中观察到的病理变化与急性（实验诱导的）去管术引入的病理变化，我们讨论了 T 管破坏作为疾病进展过程中发生的复杂兴奋-收缩耦合重塑过程的一部分的作用。最后，我们强调了 T 小管形态功能变化可能与患者基因型相关，并讨论了罕见 HCM 形式中 T 小管系统原始重塑的可能性，这些形式与编码与 T 小管结构完整性有关的蛋白质的基因相关。 ，形成和维护。