Molecular Pathways and Animal Models of Tricuspid Atresia and Univentricular Heart.

The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.

Left ventricular non-compaction in patients with single ventricle heart disease.

OBJECTIVE: Left ventricular non-compaction is an architectural abnormality of the myocardium, associated with heart failure, systemic thromboembolism, and arrhythmia. We sought to assess the prevalence of left ventricular non-compaction in patients with single ventricle heart disease and its effects on ventricular function. METHODS: Cardiac MRI of 93 patients with single ventricle heart disease (mean age 24 ± 8 years; 55% male) from three tertiary congenital centres was retrospectively reviewed; 65 of these had left ventricular morphology and are the subject of this report. The presence of left ventricular non-compaction was defined as having a non-compacted:compacted (NC:C) myocardial thickness ratio >2.3:1. The distribution of left ventricular non-compaction, ventricular volumes, and function was correlated with clinical data. RESULTS: The prevalence of left ventricular non-compaction was 37% (24 of 65 patients) with a mean of 4 ± 2 affected segments. The distribution was apical in 100%, mid-ventricular in 29%, and basal in 17% of patients. Patients with left ventricular non-compaction had significantly higher end-diastolic (128 ± 44 versus 104 ± 46 mL/m2, p = 0.047) and end-systolic left ventricular volumes (74 ± 35 versus 56 ± 35 mL/m2, p = 0.039) with lower left ventricular ejection fraction (44 ± 11 versus 50 ± 9%, p = 0.039) compared to those with normal compaction. The number of segments involved did not correlate with ventricular function (p = 0.71). CONCLUSIONS: Left ventricular non-compaction is frequently observed in patients with left ventricle-type univentricular hearts, with predominantly apical and mid-ventricular involvement. The presence of non-compaction is associated with increased indexed end-diastolic volumes and impaired systolic function.