Stirbys Petras
J Atr Fibrillation. 2016 Dec 31;9(4):1503. doi: 10.4022/jafib.1503. eCollection 2016 Dec.
Atrial fibrillation (AF) is the most challenging rhythm disturbance worldwide. Arrhythmia and its behavior represent complex pathogenesis highly opposing to contemporary curative modalities. Increasing age of patients carries a certain level of risk for AF. Some underlying diseases in concordance with aging actually accelerate the occurrence of AF. Underestimated superimposed risk factors - aging plus any known risk factor or condition (hypertension, diabetes etc.) - elicit great interest and concern. In light of these concerns we offer an elaborated universal hypothesis in attempt to elucidate the genuine origin of AF substrate. Putative chronic toxicity - toxins and/or involution related pseudo-toxins potentially generate micro- and macro-structural changes in atrial myocardium thus inciting both intracellular damage (degeneration of myocites, apoptosis) and extracellular fibrotic proliferation (interstitial fibrosis, formation of matrices, degeneration of cells with fibrotic replacement). The co-products of related underlying diseases in cooperation with cellular senescence, endogenous overproduction of specific lipids/lipoproteins and other pro-atherosclerotic and/or inflammatory components generate a total atrial response - vascular/microvascular damage, intracellular and extracellular injuries. These organizational arrangements covering the entire atrial myocardium and perhaps ganglionated plexi/autonomic branches of the nervous system eventually cause clinical havoc - atrial overstretch, atrial adaptation/maladaptation, electromechanical dysfunction, arrhythmias, heart failure, etc. In essence, valvular heart disease potentially evokes similar changes "violating" thin atrial walls to obey the same scenario. Depicted atriomyodegenerative processes most likely represent the true nature of AF substrate development. Available clinical and morphological evidence potentially designates the atriomyodegenerative or plausible neuro-atriomyodegenerative origin of AF. Deductively fusion of reasons rather than purely heterogeneity is responsible for AF induction. Thus, the uniform approach and synoptic vision of clinical and pathohistological entity may offer an alternative or refreshed viewpoint in AF substrate formation.
心房颤动（AF）是全球最具挑战性的节律紊乱。心律失常及其表现代表了与当代治疗方式高度相悖的复杂发病机制。患者年龄增长会带来一定程度的房颤风险。一些与衰老相关的潜在疾病实际上会加速房颤的发生。被低估的叠加风险因素——衰老加上任何已知风险因素或状况（高血压、糖尿病等）——引发了极大的兴趣和关注。鉴于这些问题，我们提出一个详尽的通用假说，试图阐明房颤基质的真正起源。假定的慢性毒性——毒素和/或与退化相关的假毒素可能在心房心肌中产生微观和宏观结构变化，从而引发细胞内损伤（心肌细胞变性、凋亡）和细胞外纤维化增殖（间质纤维化、基质形成、纤维化替代细胞的变性）。相关潜在疾病的共同产物与细胞衰老、特定脂质/脂蛋白的内源性过度产生以及其他促动脉粥样硬化和/或炎症成分共同产生整个心房反应——血管/微血管损伤、细胞内和细胞外损伤。这些覆盖整个心房心肌以及可能还有神经节丛/神经系统自主分支的组织变化最终导致临床紊乱——心房过度伸展、心房适应/适应不良、机电功能障碍、心律失常、心力衰竭等。本质上，瓣膜性心脏病可能引发类似变化，“侵犯”薄壁心房，遵循相同的情况。所描述的心房肌退行性过程很可能代表了房颤基质发展的真正本质。现有的临床和形态学证据可能表明房颤起源于心房肌退行性或可能的神经 - 心房肌退行性。房颤的诱发是由多种原因的演绎融合而非纯粹的异质性导致的。因此，对临床和病理组织学实体的统一方法和综合视角可能为房颤基质形成提供一个替代或全新的观点。
