Left ventricular non-compaction in childhood: echocardiographic follow-up and prevalence in first-degree relatives
Authors: Kock T , Boerresen M F , Sillesen A S , Voegg O , Norsk J B , Paerregaard M M , Vejlstrup N G , Christensen A H , Iversen K , Bundgaard H , Axelsson Raja A 
Published: October 2022

Abstract

Introduction
Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall. LVNC may be associated with reduced systolic function but is also found in individuals with normal ventricular function. It is debated whether LVNC is only congenital or may develop later in life. The clinical importance and heredity of LVNC with normal systolic function is unclear.

Purpose
We aimed to describe the echocardiographic development of the left ventricular function and LVNC pattern in children with LVNC, diagnosed at birth, at follow-up at the age of 2–4 years compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives.

Methods
A follow-up transthoracic echocardiography was performed in children at 2–4 years of age, diagnosed with LVNC at birth (&lt;30 days) as part of a large population study of newborns (n&gt;25,000). Cases were matched 1:4 to controls on mother's age at delivery, parity, and age of the child at follow-up. First-degree relatives (parents, siblings and half-siblings) of cases and controls were also offered inclusion. LVNC was defined as a ratio of non-compact to compact myocardium of ≥2 in at least one left ventricular segment measured in end-diastole perpendicular to the left ventricular cavity.

Results
13 of the 16 children diagnosed with LVNC at birth (median age 3 (interquartile range (IQR) 3–4) years, 77% male) and 52 children without LVNC at birth (age 4 (IQR 3–4) years, 88% male) was reevaluated as well as 36 first-degree relatives of children with LVNC (age 30 (IQR 4–37) years, 44% male) and 136 first-degree relatives of children without LVNC (age 32 (IQR 10–38) years, 50% male). In probands, the number of segments fulfilling criteria (8% vs. 13%, p=0.4) and systolic function, measured as fractional shortening (FS), were unchanged from birth to follow-up, and within normal range (29% vs. 30%, p=0.34). However, at follow-up, FS was significantly lower in probands compared with matched controls (30% vs. 33%, p&lt;0.001). Criteria of LVNC was fulfilled in 11 out of 36 (31%) first-degree relatives to probands, whereas none of the first-degree relatives of children without LVNC fulfilled criteria of LVNC (p&lt;0.001). FS was significantly lower in first-degree relatives of probands fulfilling criteria of LVNC compared to first-degree relatives of matched controls (30% vs. 32%, p=0.01).

Conclusion
Children with LVNC diagnosed neonatally as part of a population study still had a reduced systolic function when compared to controls but showed no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2–4 years. One third of first-degree relatives to children diagnosed with LVNC with a preserved systolic function, fulfilled criteria for LVNC and had reduced systolic function compared to controls. These findings strongly support family-screening and clinical follow-up of children with LVNC.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk FoundationHerlev-Gentofte Hospital Internal Funding