State-of-the-Art Review Article
Left Ventricular Noncompaction: A 25-Year Odyssey

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Left ventricular noncompaction (LVNC) is a cardiomyopathy associated with sporadic or familial disease, the latter having an autosomal dominant mode of transmission. The clinical features associated with LVNC vary from asymptomatic to symptomatic patients, with the potential for heart failure, supraventricular and ventricular arrhythmias, thromboembolic events, and sudden cardiac death. Echocardiography is the diagnostic modality of choice, revealing the pathognomonic features of a thick, bilayered myocardium; prominent ventricular trabeculations; and deep intertrabecular recesses. Widespread use and advances in the technology of echocardiography and cardiac magnetic resonance imaging are increasing awareness of LVNC, and cardiac magnetic resonance imaging is improving the ability to stage the severity of the disease and potential for adverse clinical consequences. Study of LVNC through research in embryology, imaging, and genetics has allowed enormous strides in the understanding of this heterogeneous disease over the past 25 years.

Section snippets

History of Left Ventricular Noncompaction

References to a spongy or embryonic myocardium, particularly in association with complex congenital heart disease, have been made in the pathology literature periodically for more than 80 years.30 The historical aspects of LVNC have been well described in the literature.31 The histology of persistence of spongy myocardium with embryonic blood supply was first discussed in the literature in 197532 and subsequently described as spongy myocardium with persistent sinusoids in the 1980s.33, 34 In

Embryology

Detailed description of the embryonic development of the ventricular myocardium is beyond the scope of this review. This has been elegantly described in the literature.1, 2, 3, 4, 5, 31 Briefly, at 5 to 8 weeks of normal embryonic development, intertrabecular recesses or “sinusoids” form. The recesses are in direct communication with the LV endocardium. As normal cardiac development progresses and myocardial compaction occurs, the intertrabecular recesses transform into capillary beds.3, 31 The

Diagnostic Criteria and Differential Diagnosis

Several echocardiographic and magnetic resonance imaging definitions for the diagnosis of LVNC have been proposed and used in published studies (Table 1).7, 14, 19, 22, 23, 24, 25, 26 Two-dimensional echocardiography has been the foundation for establishing diagnosis, increasing awareness and better delineating the phenotypic expressions of LVNC (Figures 3 and Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Videos 1–7;

view video clips online). CMR is a complementary imaging

Echocardiography Caveats: Tricks and Tips

Our approach to diagnosing LVNC includes an evaluation of the trabeculations’ sizes (noncompacted myocardium) in relation to compacted wall thicknesses in multiple imaging windows and at different ventricular levels during different phases of the cardiac cycle. We diligently search for identification of the bilayered myocardium (compacted and noncompacted) in the short-axis views at the mid and apical levels and in the apical four-chamber and apical long-axis views. The thicknesses of the

Racial and Gender Prevalence in Left Ventricular Noncompaction

The gender and racial prevalence of LVNC are heterogeneous and uncertain.27, 28, 29 This uncertainty is reinforced by variable reports in the literature suggesting polar opposite conclusions: a study of African and Arab patients found women to have a higher prevalence of LVNC.27 An alternative study in adults with LVNC found that there was a higher prevalence in men, without differences in clinical, neurologic, echocardiographic, and electrocardiographic parameters or prognosis.27, 28

The true

Genetics of Left Ventricular Noncompaction

Understanding of LVNC genetics is evolving, with evidence of both sporadic and familial cases, the latter having an autosomal dominant mode of transmission.15, 16, 17, 18 These genetic insights, epigenetic factors, and pathophysiologic mechanisms are being actively investigated for a better understanding of how to prevent and treat the major complications associated with this entity. The most common mutations occur in cardiac sarcomeric proteins such as β-myosin heavy chain.15, 16, 17, 18, 49,

Clinical Spectrum of Left Ventricular Noncompaction and Complex Clinical Decisions

LVNC is an increasingly recognized cardiomyopathy with natural history complicated by arrhythmias, thromboembolism, HF, and death.9, 10 Incidental and familial discovery of LVNC has been associated with high probability of a stable course over several years, whereas patients with symptoms of HF, histories of sustained ventricular tachycardia, or enlarged left atria have an unstable clinical course and a grave prognosis.60 Mortality does not differentiate patients with isolated LVNC from those

In Search of Clarity: Future Directions

Awareness of LVNC as a distinct morphologic entity in echocardiography laboratories is the first step toward elucidating a strategy to diagnose and understand the spectrum and natural history of LVNC. Echocardiography is the diagnostic modality of choice, and high priority should be given to establishing a standard nomenclature and unified diagnostic criteria for clinical practice and for future research as the foundation of knowledge of LVNC. The use of novel 2D and 3D echocardiography-derived

Conclusions

LVNC appears to be a distinct cardiomyopathy with marked genetic heterogeneity. LVNC results from an arrest of normal ventricular myocardial maturation by heretofore unknown molecular mechanisms. The resulting bilayered ventricular myocardium is prone to LV diastolic and systolic dysfunction, HF, arrhythmias, and thromboembolic complications. The management of the protean manifestations of the disease first requires an accurate diagnosis. The distinct morphologic features of LVNC cardiomyopathy

Acknowledgments

We gratefully acknowledge Barbara Danek, Joe Grundle, and Katie Klein for editorial preparation of this review and Brian Miller and Brian Schurrer for their help in preparing the illustrations.

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