# Left Ventricular Non-Compaction Cardiomyopathy-Still More Questions than Answers
## 2 Pathogenesis  
The pathogenesis of LVNC is not undoubtedly established. The \"theory of non-compaction\" is the most accepted since [PERSON] used for the first time the term \"isolated noncompaction of the left ventricular myocardium\" and proposed the possible mechanism [3]. According to this theory, disturbances in the normal development of the heart muscle lead to the persistence of hypertrabeculation at the cost of a thin compact subepicardial layer. In the complex process of human heart development, trabeculations appear in the cardiac jelly at the end of 4 weeks of gestation, forming spongy structures protruding in the ventricular lumen. At this time, coronary circulation does not exist yet, the highly developed trabecular structure of the endocardial part of the ventricular wall ensures sufficient oxygen supply. The thin subepicardial part of the heart muscle forms the \"compacted myocardium\" while the trabecular part forms the \"non-compacted\" part. In the next weeks, the trabeculae thicken increasing the volume of the compacted layer while intertrabecular recesses compress and form capillaries [17]. The disturbances of this process, whatever the reason, lead to the persistence of hypertrabeculation and LVNC. However, one can expect that during the compaction process a rapid decrease in the trabeculae volume and an increase in the compacted layer volume should be present. Unfortunately, such a process was documented only in chickens, but not in humans [18; 19]. [PERSON] et al. performed a meta-analysis of 31 papers dealing with human ventricle development [20]. Despite inconsistent data and different measurement methods used, it seems to be certain that the growth of the trabeculae is constant throughout the development phase. A decrease in trabeculae volume could not be documented in humans and the authors concluded that there is no evidence for the compaction process in humans. Excessive proliferation of trabeculae was observed in mice after the introduction of a genetic variant of human LVNC resulting in the development of the LVNC phenotype [21; 22]. This supports the idea that the LVNC phenotype and increased NC/C ratio are caused by the proliferation of trabeculae, but not as a result of compaction disturbances [6]. The hypertrabeculation was observed in humans as an adaptive phenomenon to increased cardiac output in athletes, pregnant women between the first and third trimester, and patients with hemoglobinopathy [6]. The physiological effect of hypertrabeculation remains controversial. The trabeculated ventricle can work more efficiently generating the same stroke volume at lower strain and wall stress. Moreover, hypertrabeculation can be reversible as seen in pregnant women, which supports its adaptive role. Hypertrabeculation observed in African athletes, however, together with a slight decrease in EF, was not a sign of pathological remodeling [12]. [PERSON] et colleagues found decreased circumferential strain in patients with a higher degree of trabeculation [13]. The \"theory of non-compaction\", however very attractive and convincing, is not confirmed in available publications. This does not necessarily mean that the theory is false. Perhaps we are dealing with a disease that has many etiologies, and the only common denominator is the excessive trabecular phenotype.