Noncompaction cardiomyopathy and heterotaxy syndrome

Abstract

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by compact and trabecular layers of the left ventricular myocardium. This cardiomyopathy may occur with congenital heart disease (CHD). Single cases document co-occurrence of LVNC and heterotaxy, but no data exist regarding the prevalence of this association. This study sought to determine whether a non-random association of LVNC and heterotaxy exists by evaluating the prevalence of LVNC in patients with heterotaxy. In a retrospective review of the Indiana Network for Patient Care, we identified 172 patients with heterotaxy (69 male, 103 female). Echocardiography and cardiac magnetic resonance imaging results were independently reviewed by two cardiologists to ensure reproducibility of LVNC. A total of 13/172 (7.5%) patients met imaging criteria for LVNC. The CHD identified in this subgroup included atrioventricular septal defects [11], dextrocardia [10], systemic and pulmonary venous return abnormalities [7], and transposition of the great arteries [5]. From this subgroup, 61% (n = 8) of the patients developed arrhythmias; and 61% (n = 8) required medical management for chronic heart failure. This study indicates that LVNC has increased prevalence among patients with heterotaxy when compared to the general population (0.014–1.3%) suggesting possible common genetic mechanisms. Interestingly, mice with a loss of function of Scrib or Vangl2 genes showed abnormal compaction of the ventricles, anomalies in cardiac looping, and septation defects in previous studies. Recognition of the association between LVNC and heterotaxy is important for various reasons. First, the increased risk of arrhythmias demonstrated in our population. Secondly, theoretical risk of thromboembolic events remains in any LVNC population. Finally, many patients with heterotaxy undergo cardiac surgery (corrective and palliative) and when this is associated with LVNC, patients should be presumed to incur a higher peri-operative morbidity based on previous studies. Further research will continue to determine long-term and to corroborate genetic pathways.

Left Ventricular Noncompaction—A Systematic Review of Risk Factors in the Pediatric Population

“…However, a large meta-analysis concerning the survival of children with isolated LVNC, as well as those with coexisting CHD, is necessary to draw clear conclusions, as comparing mortality and transplantation rates from 16 studies showed no significant differences between the two groups. It is of note that LVNC has been reported to occur more frequently among children with heterotaxy syndrome, with a prevalence of 7.5% vs. 0.013–1.3% in the general population, which may suggest a common genetic mechanism [ 56 ].…”

Left Ventricular Noncompaction in a Child with Turner Syndrome

“…LVNC is a genetic cardiomyopathy characterized by left ventricular prominent trabeculations and sinusoids communicating with its cavity. It may be isolated or may occur in conjunction with other CHD such as stenotic diseases of left ventricular outflow tract, Ebstein's anomaly, septal defects, and tetralogy of Fallot [8].…”

Clinical Insights Into Heritable Cardiomyopathies

“…LVNC also shows increased incidence in certain physiologic states, such as pregnancy ( Gati et al, 2014 ) and vigorous physical activity ( Gati et al, 2013 ; de la Chica et al, 2020 ). It is also seen in association with other conditions such as in patients with congenital heart disease (CHD), neuromuscular disorders, mitochondrial disease and metabolic derangements ( Finsterer et al, 2017 ; Martinez et al, 2017 ; Ross et al, 2020 ; Vershinina et al, 2020 ). Since the initial description in 1926, LVNC has been coined with various names, including spongiform myocardium, fetal or primordial myocardium, hypertrabeculation syndrome, and non-compaction cardiomyopathy ( Maron et al, 2006 ; Engberding et al, 2007 ).…”

“…Without analytic and universally accepted criteria, the prevalence of LVNC is difficult to estimate, but the approximate range is estimated in the 0.014–1.3% range of patients undergoing echocardiography ( Pignatelli et al, 2003 ; Stanton et al, 2009 ). However, among patients with heart failure and patients with severe CHD, the prevalence has been reported at around 4 and 7.5%, respectively ( Kovacevic-Preradovic et al, 2009 ; Martinez et al, 2017 ). In this review, we provide an informative categorization of 9 distinct subphenotypes of LVNC ( Towbin and Beasley, 2020 ) ( Table 5 ).…”