Lack of morphometric evidence for ventricular compaction in humans

Abstract

The remodeling of the compact wall by incorporation of trabecular myocardium, referred to as compaction, receives much attention because it is thought that its failure causes left ventricular noncompaction cardiomyopathy (LVNC). Although the notion of compaction is broadly accepted, the nature and strength of the evidence supporting this process is underexposed. Here, we review the literature that quantitatively investigated the development of the ventricular wall to understand the extent of compaction in humans, mice, and chickens. We queried PubMed using several search terms, screened 1127 records, and selected 56 publications containing quantitative data on ventricular growth. For humans, only 34 studies quantified wall development. The key premise of compaction, namely a reduction of the trabecular layer, was never documented. Instead, the trabecular layer grows slower than the compact wall in later development and this changes wall architecture. There were no reports of a sudden enlargement of the compact layer (from incorporated trabeculae), be it in thickness, area, or volume. Therefore, no evidence for compaction was found. Only in chickens, a sudden increase in compact myocardial thickness layer was reported coinciding with a decrease in trabecular thickness. In mice, morphometric and lineage tracing investigations have yielded conflicting results that allow for limited compaction to occur. In conclusion, compaction in human development is not supported while rapid intrinsic growth of the compact wall is supported in all species. If compaction takes place, it likely plays a much smaller role in determining wall architecture than intrinsic growth of the compact wall.

New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function

“…The association between the formation of the PF network and trabecular compaction may explain differences of PF localization between the chick and the mouse. The presence of deep PF in the chick would originate from extensive trabecular compaction in comparison to the mouse in which trabecular compaction is restricted to subendocardial cardiomyocytes [107][108][109]. PF network morphogenesis is thus integrally related with ventricular maturation potentially explaining conduction defects associated with congenital malformations or inherited cardiomyopathies.…”

Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation

“…Trabecular formation begins in the embryo in the early stages of chamber development under the influence of growth factors from the endocardium and transcription factors that are broadly expressed in the myocardium (Del Monte‐Nieto et al, 2018 ; Rhee et al, 2018 ; Sedmera et al, 2000 ; Sizarov et al, 2011 ; Stennard et al, 2003 ; Wilsbacher & McNally, 2016 ). Accordingly, trabecular volumes of both ventricles undergo a pronounced increase and they are therefore positively correlated in this period (Blausen et al, 1990 ; Faber et al, 2021b ). Important developmental processes impact differently on the two ventricles, however.…”

“…Noncompaction is the hypothesized aetiology defined as a failure of compaction (Chin et al, 1990 ), where compaction itself is a process originally described in chicken whereby embryonic trabeculation coalesce to become compact wall (Rychterova, 1971 ). To date, however, no hard evidence exists for compaction in human (Faber et al, 2021b ). Instead, trabeculations can be measured to grow throughout gestation (Blausen et al, 1990 ; Faber et al, 2021a , 2021c ) rather than exhibiting the decrease in volume that would be expected if they coalesced into compact wall (Faber et al, 2021b ).…”

“…To date, however, no hard evidence exists for compaction in human (Faber et al, 2021b ). Instead, trabeculations can be measured to grow throughout gestation (Blausen et al, 1990 ; Faber et al, 2021a , 2021c ) rather than exhibiting the decrease in volume that would be expected if they coalesced into compact wall (Faber et al, 2021b ). In this study, therefore, we prefer the term ‘excessive trabeculation’ as introduced by (Anderson et al, 2017 ).…”

Differential Growth Rates, Rather Than Compaction, Determine Left Ventricular Wall Formation

“…16,17 ), or even up to birth 18 . Nevertheless, there are no comprehensive quantitative assessments of compact and trabecular layer growth to support the notion of compaction 19 . In fact, only two studies have quanti ed the trabecular layer volume in embryonic development and both report a continuous increase and not a decrease as would be expected if compaction was to occur (see 19 ).…”