Jeffrey A. Towbin

Chapter Outline

Pathology of Left Ventricular Noncompaction

In the early embryo, the heart is a loose interwoven mesh of muscle fibers.10,11 The developing myocardium gradually condenses, and the large spaces within the trabecular meshwork disappear, condensing and compacting the ventricular myocardium and solidifying the endocardial surfaces. Trabecular compaction is normally more complete in the LV than in the right ventricular (RV) myocardium. The situations in which this compacting pathway fails is thought to be due to an arrest in endomyocardial morphogenesis and results in postnatal LV noncompaction.^4,10,11 The gross pathologic appearance of LVNC is characterized by numerous, excessively prominent trabeculations and deep intratrabecular recesses resembling RV endomyocardial morphology. Histologically, the recesses and their troughs are lined with endothelium, indicating that these recesses are not sinusoids. In some cases, zones of fibrous and elastic tissue are found scattered on the endocardial surfaces with extension into the recesses. The coronary arterial circulation is usually normal, and extramural myocardial blood supply is not believed to play a role in these abnormalities. Intramural perfusion, however, could be adversely affected by the prominent trabeculations and intratrabecular recesses, particularly the subendocardium. The increased fibrous and elastic tissue on the endocardial surfaces could be due to subendocardial ischemia, perhaps in response to isometric contraction among the trabeculae and recesses. In addition, the endomyocardial morphology of LVNC lends itself to development of mural thrombi within the recesses, which can embolize and cause a stroke.^2,8,12,13 Arrhythmias can also occur.^14–16

Incidence of Left Ventricular Noncompaction

Although LVNC is considered rare by some authors, the incidence and prevalence of LVNC is uncertain.17–20 In the 1990s, the reported prevalence of isolated LVNC was 0.05% of all adult echocardiographic examinations in a large institution, whereas more recently the prevalence was reported as less than 0.14% of all adults referred for echocardiograms. In contrast, Sandhu et al.¹⁷ demonstrated a 3.7% prevalence of definite or probable LVNC by echocardiography in adults with LVEF less than or equal to 45% and 0.26% prevalence for all patients referred for echocardiography. Among heart failure patients, the prevalence of LVNC has been reported as 3% to 4%.²⁰ No other reliable data have been reported to date.

Clinical Features and Diagnosis of Left Ventricular Noncompaction

The clinical presentation of LVNC is highly variable, ranging from asymptomatic to end-stage heart failure, lethal arrhythmias, or thromboembolic events.2–7,12–17 LVNC commonly develops in infancy with signs and symptoms of heart failure.^2,4,7 Childhood and adult forms are also frequently seen and can occur with heart failure, rhythm abnormalities, or sudden death.^12,13,19,20 However, a high percentage of patients are asymptomatic and identified serendipitously on echocardiography, with deep trabeculations and intertrabecular recesses noted in the LV apex and lateral wall. Multiple forms of LVNC exist and the clinical features depend on the specific form of LVNC (discussed later).

In addition to systemic arterial embolism, patients with LVNC are also known to develop ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), atrial fibrillation, or conduction abnormalities (sinus bradycardia, complete heart block). Wolff-Parkinson-White syndrome is also common.2,7 Reports of survival in children and adults have been inconsistent, with some demonstrating poor outcomes and others having a low percentage of death or transplantation. For example, Ichida et al.⁷ found good survival and limited symptoms in their childhood patients, whereas Chin et al.⁴ reported three deaths in the eight children studied. Pignatelli et al.² demonstrated poor outcomes in neonates but excellent outcomes in those outside the neonatal period. The neonates who died all had systemic disease (mitochondrial and other metabolic disorders); they demonstrated a 5-year survival rate of 86%. When patients receiving transplants were added, the 5-year survival free of death or transplantation was 75%.

Adult clinical studies consistently have described a high risk of ventricular tachyarrhythmias and sudden cardiac death (SCD) in LVNC,1,13,15 with as many as 47% of adults (and 75% of symptomatic patients) dying within 6 years of presentation. More recent reports, however, have shown a more benign natural history, with lower risk for (malignant) ventricular arrhythmias.²¹ Bhatia et al.²² reviewed published studies of 241 adults with isolated LVNC diagnosed by echocardiographic criteria followed for a mean duration of 39 months. The annualized event rate was 4% for cardiovascular deaths, 6.2% for cardiovascular death and its surrogates (heart transplantation and appropriate ICD shocks), and 8.6% for all cardiovascular events (death, stroke, ICD shocks, and transplantation). Familial LVNC occurrence was identified in first-degree relatives screened by echocardiography in 30% of index cases.²² The precise substrate for malignant ventricular arrhythmias in LVNC patients is not known,²³ and the progression of the disease and evolution of the arrhythmic substrate remains speculative. Histologic examination shows myocardium around deep intratrabecular recesses that can serve as slow conducting zones with reentry. Furthermore, impaired flow reserve, causing intermittent ischemia, has been proposed as having a role²⁴; however, inducibility of sustained ventricular tachycardia (VT) during electrophysiological studies has demonstrated little value as a tool for risk stratification in LVNC.^14,23

Subtypes of Left Ventricular Noncompaction

Although an increasing number of clinicians are beginning to recognize the clinical features of LVNC, several key points have failed to be described. One of the important issues in the diagnosis and outcomes of these patients, particularly in childhood, is the specific LVNC phenotype that exists in any one subject. There are at least seven different phenotypes of LVNC and these different phenotypes have different outcomes (Figure 90-1). The subtypes include the following types: