Arrhythmias and Conduction Disturbances in Noncompaction Cardiomyopathy

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This chapter discusses the form of cardiomyopathy known as left ventricular noncompaction cardiomyopathy (LVNC), with a specific focus on the arrhythmias associated with LVNC. This presentation of heart disease carries a substantial risk for heart failure, stroke, metabolic derangement, arrhythmias, and sudden cardiac death (SCD). It can present at any age and appears to be a result of mutations in genes identified to encode primarily for cytoskeletal or sarcomeric proteins. It seems be a continuum with other cardiomyopathies.

Characterized by excessive and unusual trabeculation of the mature left ventricle (LV), LVNC has been considered to occur because of arrest of the final phase of cardiac development, the compaction phase, during which the compact myocardium fully forms. Clinically and pathologically, LVNC is characterized by a spongy morphologic appearance of the myocardium, with abnormal trabeculations and intertrabecular recesses typically being most evident in the apical portion of the LV. ^,

In 2006, the American Heart Association (AHA) scientific statement on the classification of cardiomyopathies formally classified LVNC as its own disease entity. The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases, however, continues to consider LVNC to be a trait rather than a specific disease but recommends genetic analysis when a diagnosis is made. ^, Indeed, multiple forms of LVNC occur, including the dilated cardiomyopathy (DCM) form of LVNC, the hypertrophic cardiomyopathy (HCM) form, and noncompaction associated with congenital heart diseases (CHDs), such as atrial septal defects (ASDs) or ventricular septal defects (VSDs), pulmonic stenosis (PS), Ebstein anomaly, and hypoplastic left heart syndrome (HLHS), among others. In all forms, metabolic derangements may be notable. ^,

Pathology

In the early embryo, the heart is a loose interwoven mesh of muscle fibers. The developing myocardium gradually condenses, and large spaces within the trabeculation 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 are thought to be because of an arrest in endomyocardial morphogenesis and result in postnatal LV noncompaction. ^, The gross pathologic appearance of LVNC is characterized by numerous, excessively prominent trabeculations and deep intertrabecular 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 fibrosis 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 could be adversely affected by the prominent trabeculations and intertrabecular recesses, particularly in the subendocardium. The abnormal endocardial fibrous and elastic tissue will result in abnormal mechanics, causing the apex and bases to rotate in the same direction, without the normal twisting contraction of the heart. The endomyocardial morphology of LVNC lends itself to the development of mural thrombi within the recesses, which can embolize and cause strokes. ^{, ,} Arrhythmias can be acquired or can occur because of the associated pathology. The precise mechanism for malignant ventricular arrhythmias in LVNC patients is not known. Histologic examination demonstrates myocardium around the deep intertrabecular recesses that may serve as areas of slow conduction and substrate for reentry. Furthermore, impaired flow reserve, causing intermittent ischemia, has been proposed as having a role.

Incidence

Although LVNC is considered rare by some authors, the incidence and prevalence of LVNC is uncertain because of changing diagnostic criteria. Further, it has been realized that many patients are asymptomatic, making it almost impossible to describe the real incidence if no data from population studies are available. 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. demonstrated a 3.7% prevalence of definite or probable LVNC by echocardiography in adults with LV ejection fraction (EF) of 45% or less and a 0.26% prevalence for all patients referred for echocardiography. Among heart failure patients, the prevalence of LVNC has been reported as 3% to 4%. In a registry of pediatric cardiomyopathy patients, noncompaction was discovered in 5% of registered children. Overdiagnosis and underdiagnosis of LVNC has been questioned by some because of the lack of precision of the current diagnostic criteria, and it has also been suggested that African Americans and athletes may show a high prevalence of LV hypertrabeculation.

Clinical Features and Diagnosis

The clinical presentation of LVNC is highly variable, ranging from asymptomatic to end-stage heart failure, lethal arrhythmias, or thromboembolic events. ^{, ,} LVNC may exist as isolated disease, but it may also be associated with HCM and DCM.

In infancy, LVNC commonly develops with signs and symptoms of heart failure. Childhood LVNC can occur with heart failure, rhythm abnormalities, or SCD. ^{, , ,} Ichida et al. found good survival and limited symptoms in their childhood patients, whereas Chin et al. reported three deaths in eight children studied. Pignatelli et al. demonstrated poor outcomes in neonates but excellent outcomes in those outside the neonatal period. All of the neonates who died had systemic disease (mitochondrial and other metabolic disorders), and 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%.

The same specter of arrhythmia, heart failure, and thrombosis is described in adults. Nevertheless, 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. It may be advisable to use multimodality imaging (valid echocardiographic criteria, speckled tracking, and cardiac magnetic resonance imaging [CMR]) to confirm the diagnosis based on the ratio of compacted to noncompacted layers and on the nontrabeculated mass. ^,

Patients with LVNC are known to develop ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), atrial fibrillation (AF), and conduction abnormalities (sinus bradycardia and complete heart block). Ventricular preexcitation is also common (presenting in more than 10% of LVNC patients). ^{, , ,}

Reports of survival have been inconsistent. Adult clinical studies consistently describe a high risk for ventricular tachyarrhythmias and SCD in LVNC, ^{, ,} 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. Bhatia et al. reviewed published studies, including 241 in adults with isolated LVNC diagnosed by echocardiographic criteria followed for a mean duration of 59 months. The annualized event rate was 4% for cardiovascular deaths, 6.2% for cardiovascular death and its surrogates (heart transplant, inappropriate implantable cardioverter-defibrillator [ICD] shocks), and 8.6% for all cardiovascular events (death, stroke, ICD shocks, and transplantation). Echocardiographic screening of first-degree family members identified familial LVNC for 30% of index cases. This was confirmed by Caliskan et al. who also showed that the majority of these patients were asymptomatic, in spite of mild to moderate LV dysfunction. Testing for inducibility of sustained VT during electrophysiologic (EP) studies has demonstrated little value as a tool for risk stratification in LVNC. ^, An electrocardiographic (ECG) finding suggestive of potential for reentry is the presence of QRS notches (QRS fragmentation) or J waves (early repolarization), which have been frequently reported. ^{, , ,}