Left Ventricular Non-Compaction: Evolving Concepts

Abstract

Left ventricular non-compaction (LVNC) is a rare heart muscle disease defined by the presence of prominent left ventricular trabeculation, deep intertrabecular recesses, and a thin compact layer. Several hypotheses have been proposed regarding its pathogenesis, with the most recently accepted one being that compact layer and trabeculated layers develop independently according to an "allometric growth". The current gold-standard diagnostic criteria (in particular, the Petersen index non-compaction/compaction ratio > 2.3) reflect an excess of myocardial trabeculation, which is not a specific morpho-functional feature of LVNC cardiomyopathy but merely a "phenotypic trait", even described in association with other myocardial disease and over-loading conditions. Accordingly, the European Society of Cardiology (ESC) guidelines have definitively abolished the term 'LVNC cardiomyopathy'. Recently, evolving perspectives led to the restoration of LVNC cardiomyopathy by distinguishing "hypertrabeculation phenotype" and "non-compaction phenotype". It has been proposed that the disease-specific pathophysiologic mechanism is a congenitally underdevelopment of the compact layer accounting for an impairment of the left ventricular systolic function. Future prospective research should focus on the clinical and prognostic relevance of compact layer thinning rather than excessive trabeculation, which could significantly influence the management of patients with LVNC. The review aims to update current knowledge on the pathogenesis, genetics, and diagnostic criteria of LVNC, offering modern insights for future perspectives.

Keywords: cardiomyopathies; hypertrabeculation; left ventricular non-compaction; spongy myocardium.

Figure 1

Graphical illustration. The NC/C ratio > 2.3 is due to an increase of numerator (non-compact layer) or a decrease of denominator (compact layer). An increased thickness of non-compact layer is the result of excessive trabeculation. This is a normal “phenotypic trait” observed in healthy individuals with normal LV size and function or a phenotypic feature superimposed on other heart muscle disease such as dilated cardiomyopathy and overloading conditions rather than a distinctive morpho-functional marker for LVNC cardiomyopathy. A reduction of thickness of the compact layer instead defines LVNC. Based on left ventricular ejection fraction (LVEF), we distinguish a “LVNC phenotype” characterized by preserved LVEF and “LVNC cardiomyopathy” characterized by reduction of LVEF. This implies that LVNC cardiomyopathy has a peculiar disease-specific mechanism. Legend: C = compact (layer); NC = non-compaction (layer); LV = left ventricle; LVNC = left ventricular non-compaction.

Figure 2

A representative example of a patient with LVNC with LVEF reduction. Diastolic frames of kinetic images in both four-chamber long axis and three-chamber long axis views showing a thinned compact layer with a thickness < 5 mm of the free-wall mid-ventricular segments. Note the free wall to septum asymmetry of thickness. Adapted from De Lazzari et al. [90]. LVNC = left ventricular non-compaction; LVEF = left ventricular ejection fraction.

Figure 3

A representative example of a patient with LVNC with preserved LVEF. Diastolic frames of kinetic images in both four-chamber-long axis and three-chamber-long axis views showing a thickness of compact layer ≥ 5 mm. Adapted from De Lazzari et al. [90]. LVNC = left ventricular non-compaction; LVEF = left ventricular ejection fraction.