Left ventricular noncompaction − Risk stratification and genetic consideration −

Summary Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by two layered structures composed of prominent trabecular meshwork and deep intertrabecular recesses. LVNC was thought to be rare; however, heightened awareness has resulted in an increased detection of the morphological features of LVNC in routine clinical practice especially in the adult population. Although LVNC was classified as an independent primary cardiomyopathy of genetic origin by the American Heart Association in 2006, its definition, diagnostic criteria and clinical implications are still being debated. Clinical manifestations are highly variable, even in the same family, ranging from no symptoms to disabling congestive heart failure, life-threatening arrhythmias, systemic thromboemboli, and sudden cardiac death. Among phenotypic subtypes of LVNC, children with isolated LVNC with normal cardiac function had the best outcomes: children with LVNC and dilated cardiomyopathy had the worst outcomes. Myocardial dysfunction or ventricular arrhythmias are predictors of mortality in adults with LVNC. LVNC, like other forms of inherited cardiomyopathy, is genetically heterogeneous and can be inherited as an autosomal dominant or X-linked recessive disorder. It has been linked to mutations in many genes, including ZASP, TAZ/G4.5, and those encoding sarcomeric, Z-disc, cytoskeleton proteins, and mitochondria. Disturbance of the NOTCH signaling pathway has been reported to be part of genetic pathway for LVNC as well. Although there are an increasing number of reports, genotype-phenotype correlations have been challenging and investigations are ongoing. Patients with mutations are more likely to have major adverse cardiovascular events, further, LV systolic dysfunction in mutation carriers makes them at high risk for cardiac events. Treatments focus on improvement in cardiac function and reduction of mechanical stress in patients with systolic dysfunction and on treatment of arrhythmia and implantation of an automatic implantable cardioverter-defibrillator for prevention of sudden death. Given that 20–40% of cases may be familial, family screening is recommended.