**1. Introduction**

Left ventricular noncompaction (LVNC) is a unique form of cardiomyopathy that is distinguished by a distinctive ("spongy") morphological appearance of the left ventricle (LV) myocardium [1]. This "spongy" appearance encompasses hypertrabeculation, deep intertrabecular recesses or sinusoids, and a bilayered ventricular myocardium with a noncompacted endocardium and compacted epicardium [2]. Although LVNC is rare, the prevalence of LVNC is reported to be <0.3% in adults and < 0.0001% in children. It is the third most common form of inherited cardiomyopathies and accounts for 9% of all pediatric cardiomyopathy cases [3]. Prevalence was reported as 0.014–1.3% in adult patients who underwent echocardiography. In heart failure patients, the prevalence of LVNC is estimated at 3–4% [4]. LVNC is characterized as genetic, primary cardiomyopathy by the 2006 American Heart Association classification model, whereas the European Society of Cardiology has not classified LVNC as distinct cardiomyopathy due to its phenotypic heterogeneity [5, 6].

Clinical presentation of LVNC is variable, and Towbin et al. have described nine distinct subtypes: 1) benign, 2) arrhythmogenic, 3) dilated, 4) hypertrophic, 5) mixed hypertrophic and dilated, 6) restrictive, 7) right ventricular with the normal left ventricle, 8) biventricular, and 9) associated with congenital heart disease [7]. Some of the LVNC phenotypes are shown in **Figure 1**. Complications of LVNC include chronic heart failure, arrhythmias, cardioembolism, chest pain, dyspnea, syncope, myocardial infarction, and sudden cardiac death (SCD) [8]. Patients with LVNC associated with neuromuscular disease may present with exercise intolerance, fatigue, muscle pain, muscle stiffness, and muscle weakness. Heart failure associated with LVNC is often due to either systolic or diastolic ventricular dysfunction. Electrocardiogram (ECG) abnormalities are very common (88–94% and 88%, respectively) in both adult and pediatric cases. Common arrhythmias are atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, and atrioventricular block. Heart failure and arrhythmias are the greatest cause of concern for mortality in LVNC patients [9].

#### **Figure 1.**

*Echocardiographic images of heterogeneous forms of left ventricular noncompaction phenotype. A. Parasternal short-axis view of a dilated form of LVNC with trabeculations noted at the apex. B. An apical 4-chamber view with trabeculations noted at the right side of the image. C-G, Heterogeneous phenotypes associated with LVNC. LVNC with normal LV size, thickness, and function (C), dilated form of LVNC (D), hypertrophic form of LVNC (E), restrictive form of LVNC (F), biventricular LVNC (G). LV, left ventricle; RV, right ventricle; LA, left atrium, RA, right atrium.*

#### *Left Ventricular Noncompaction Cardiomyopathy: From Clinical Features to Animal Modeling DOI: http://dx.doi.org/10.5772/intechopen.101085*

The etiology, pathogenesis, and natural history of LVNC are not clearly understood. The genetic causes of LVNC are heterogeneous [10, 11], involving final common pathways initiated by primary (the sarcomere) and developmental (NOTCH pathway) genetic abnormalities, often *via* a disturbance of protein–protein binding caused by the primary genetic mutation [12]. Doppler echocardiography, cardiac magnetic resonance imaging, or LV angiography are used for the diagnosis. Due to heritable nature, patients with LVNC and at-risk first-degree relatives are recommended to undergo genetic screening and counseling [13, 14]. Clinical symptoms associated with myocardial dysfunction, significant arrhythmias, congenital heart disease, or neuromuscular disease combined with the results of genetic testing dictate the outcome and therapeutic management of LVNC [15]. Family studies and animal models are incredibly important for uncovering the genetic basis and pathways involved in this disease. In this chapter, we describe trabeculation and compaction events during cardiogenesis, morphopathological features of LVNC, and possible genetic mechanisms of LVNC. We will also describe the animal models that have been used for the study of LVNC.
