Review
Left ventricular non-compaction: Genetic heterogeneity, diagnosis and clinical course

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Abstract

Left ventricular non-compaction (LVNC) is a rare disorder that results in multiple deep trabeculations within the left ventricular myocardium. It is thought to be due in part, to an arrest of myocardial development but more recent evidence suggests that some cases may actually be acquired while other isolated cases have regressed with time.

Transthoracic echocardiography remains the imaging modality of choice for LVNC where diagnosis is based on the identification of multiple prominent ventricular trabeculations with intertrabecular spaces communicating with the ventricular cavity.

There is a broad and potentially confusing spectrum of clinical symptomatology in patients with ventricular non-compaction meaning that the primary diagnosis is often missed.

Complications such as potentially malignant arrhythmias, left ventricular failure, and cardioembolic events arising as a result of non-compaction must be treated in an attempt to decrease morbidity and mortality from this disorder. The ultimate outcome for patients remains unclear with some boasting a prolonged asymptomatic course, to others displaying a rapid deterioration of left ventricular systolic function, leading to heart transplantation or death.

In conclusion, LVNC while remaining a rare cardiomyopathy, shall probably be diagnosed with increasing frequency in the coming years because of heightened awareness about its natural history and clinical manifestations and because of the improved modalities available for cardiac imaging.

Introduction

Hypertrabeculation of the left ventricle was first recognised in 1932 [1], but left ventricular non-compaction (LVNC) officially described in 1990 [2]. LVNC results in multiple trabeculations in the left ventricular myocardium and is thought to be due, in certain cases but not invariably, to an arrest of myocardial development [3]. The left ventricle generally demonstrates impaired systolic function, with or without dilatation [2], [4] and is usually the only site of non-compaction with biventricular involvement occurring in less than 50% of cases [5], [6].

Congenital heart disease is absent, by definition, in patients with the isolated form of the disease. LVNC existing in association with congenital heart diseases [7] such as ventricular septal defects, double-orifice mitral valve, [8] Ebstein's anomaly of the tricuspid valve, [9] and bicuspid aortic valve, [10] is referred to as non-isolated left ventricular non-compaction or alternatively as left ventricular non-compaction associated with congenital heart disease.

Section snippets

Prevalence

Several landmark case series of LVNC have been published in the literature. Most importantly, the series by Chin et al. [2], El-Menyar et al. [11], Ritter et al. [12], Ichida et al. [3], Oechslin et al. [13], Ross et al. [14], and Stöllberger et al. [15], [16] Male subjects tend to predominate among the published cases [17] in human beings, presumably as a consequence of underlying patterns of inheritance and gender-related differences in the prevalence and severity of symptoms which then

Embryology

Understanding the possible pathogenetic mechanisms that lead up to LVNC necessitates a clear understanding of the developmental sequence of events which take place in the embryonic heart.

The morphogenesis of a four-chambered heart commences with the formation of a linear myocardial tube lined by endocardium. The heart tube comes into existence following the medial migration and later coalescence of cardiogenic primordia arising from the splanchnopleuric mesoderm. The progenitor cells derived

Genetics

Over recent years, LVNC was found to harbor a complex and heterogeneous genetic undertone. There is mounting evidence for a role of the following genes in the aetiology of this condition:

  • 1)

    TAZ/G4.5: Bione et al. [25] identified the tafazzin gene in the q28 region of the X chromosome (TAZ, G4.5) as a disease-causing gene implicated in LVNC in addition to being the culprit gene in a wide spectrum of other severe infantile cardiomyopathies including X-linked endocardial fibroelastosis and dilated

Presentation

LVNC may present with depressed systolic function of the non-compacted left ventricle resulting in heart failure. The degree of systolic dysfunction is related to the extent of non-compaction. Alternatively it may present with cardiac arrhythmias and conduction defects including atrial fibrillation, ventricular arrhythmias which may sometimes be fatal, atrio-ventricular or bundle-branch blocks and Wolff–Parkinson–White syndrome [11]. In the series by Oechslin et al. [13] ventricular tachycardia

Diagnosis

Various imaging techniques have been employed in the diagnosis of LVNC including, but not limited to, 2-Dimensional transthoracic echocardiography, contrast-enhanced 2-Dimensional echocardiography, ventriculography, [38] ultrafast computed tomography and Cardiac Magnetic Resonance Imaging. Nevertheless, transthoracic echocardiography supplanted by the use of harmonic imaging and contrast agents in difficult cases, remains the imaging modality of choice for LVNC.

The multiple prominent

Management

Any complication or symptom arising as a result of LVNC must be treated in an attempt to decrease morbidity and mortality from this disorder. Arrhythmias are treated with beta-blockers, calcium channel blockers, amiodarone or other agents depending on the case. In one study by Toyono et al. [34] carvedilol caused a major improvement in a four month old infant with LVNC complicated by congestive heart failure. Carvedilol demonstrated beneficial effects on left ventricular function, mass and

Prognosis

The ultimate outcome for patients with LVNC remains unclear. The prognosis, as previously stated, may range from a prolonged asymptomatic course to a rapid deterioration in left ventricular systolic function leading to heart transplantation or death. Generally in both adult and pediatric populations the prognosis is persistently better in asymptomatic subjects. It is fair to say that overall however, the prognosis is poor and in the series by Oechslin et al. 50% of adult patients (6 out of 12)

Conclusion

Non-compaction of the left ventricle belonged to the group of unclassified cardiomyopathies according to the 1995 World Health Organization (WHO)/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies [61]. More recently the American Heart Association 2006 Classification, lists LVNC among the group of Genetic Cardiomyopathies [62].

While remaining a rare condition, the diagnosis of LVNC shall invariably be made with increasing

Acknowledgements

The authors would like to thank Prof. Peter Buser from the Department of Biomedicine, University Hospital, Basel, Switzerland for kindly providing access to Cardiac Magnetic Resonance images depicting a typical case of left ventricular non-compaction.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [63].

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