Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review

Abstract

Background and objective: Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by excessive trabecular formation and deep recesses in the ventricular wall, with a bilaminar structure consisting of an endocardial noncompaction layer and an epicardial compacted layer. Although genetic variants have been reported in patients with LVNC, understanding of LVNC and its pathogenesis has not yet been fully elucidated. We addressed the latest findings on genes reported to be associated with LVNC morphogenesis and possible pathologies to understand the diverse spectrum between genotype and phenotype in LVNC. Also, the latest findings and issues related to the diagnosis of LVNC were summarized.

Methods: This article is written as a commentary narrative review and will provide an update on the current literature and available data on common forms of LVNC published in the past 30 years in English through to May 2022 using PubMed.

Key content and findings: Familial forms of LVNC are frequent, and autosomal dominant mode of inheritance has been predominantly observed. Several of the candidate causative genes are also mutated in other cardiomyopathies, suggesting a possible shared molecular and/or cellular etiology. The most common gene functions were sarcomere function whereas genes in mice LVNC models were involved in heart development. Echocardiography and cardiac magnetic resonance imaging (CMR) are useful for diagnosis although there are no unified criteria due to overdiagnosis of imaging, poor consistency between techniques, and lack of association between trabecular severity and adverse clinical outcomes.

Conclusions: This review reflects the current lack of clarity regarding the pathogenesis and significance of LVNC and showed the complexity of imaging diagnostic criteria, interpretation of the role of LVNC as a cause, and uncertainty regarding the specific genetic basis of LVNC.

Keywords: Left ventricular noncompaction (LVNC); genotype; phenotype.

Figure 1

Schema of the formation (upper) and pathway (left lower) of ventricular trabeculation and compaction. The interactive regulation of endocardial, myocardial, and epicardial signaling networks is crucial to the ventricular trabeculation and compaction. BMP, bone morphogenetic protein; BMPR, bone morphogenetic protein receptor; TET, ten-eleven translocation; RA retinoic acid.

Figure 2

Characteristics of left ventricular noncompaction by echocardiography. (A) Four-chamber view image; (B) left ventricular long axis image; (C) left ventricular short axis image; (D) left ventricular short axis image with color Doppler view. (A,B) Prominent trabeculation and deep gaps are observed in the left ventricle. (C) The ventricular wall has a two-layered structure with noncompacted and compacted layers. (D) Color Doppler shows the blood flow between the recesses. LV, left ventricle; LA, left atrium; RV, right ventricle; RA, right atrium; NC, noncompacted layer; C, compacted layer.

Figure 3

Characteristics of left ventricular noncompaction by cardiac magnetic resonance imaging. Normal case (upper row) and patient with left ventricular noncompaction (lower row). Compared to normal patients, patients with left ventricular noncompaction show marked trabecular formation of the left ventricle. LV, left ventricle.

Figure 4

Summary of predominant phenotypic features in patients with LVNC. LVNC, left ventricular noncompaction; CHD, congenital heart disease; RBBB, right bundle branch block; fQRS, fragmented QRS; LVPWC, thickness of compacted layer of left ventricular posterior wall; N/C, noncompacted to compacted layer; PW, posterior wall; LVEF, left ventricular ejection fraction; LVDD, left ventricular diastolic diameter; CHF, chronic heart failure; FaH, family history; VT, ventricular tachycardia.