UNASSIGNED: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the left ventricular (LV) wall.
UNASSIGNED: The authors aimed to examine changes in LV function and morphology in 2 to 4-year-old children with and without LVNC at birth and to describe the prevalence of LVNC in first-degree relatives.
UNASSIGNED: Echocardiograms in children with and without LVNC (matched 1:4) were performed at 2 to 4 years and in first-degree relatives. LVNC was blindly assessed and defined as a ratio of non-compact to compact myocardium of ≥2 in ≥1 LV segment. Trabeculations were expressed as a percentage of the number of segments with LVNC out of the total number of segments.
UNASSIGNED: In total, 14 (median age 3 years, 71% male) of 16 children with LVNC at birth and 56 children without (median age 4 years, 71% male), 37 first-degree relatives of children with LVNC (median age 31 years, 46% male) and 146 first-degree relatives of children without (median age 33 years, 50% male) were included. In children with LVNC, trabeculation (8% vs 13%, P = 0.81) and LV ejection fraction (50% vs 49%, P = 0.91) were unchanged from birth to follow-up but LV ejection fraction was lower compared to children without LVNC (49% vs 60%, P < 0.001). In relatives of children with LVNC, 11 of 37 (30%) fulfilled LVNC criteria compared to no relatives to children without LVNC (P < 0.001).
UNASSIGNED: At 2 to 4 years, children with LVNC diagnosed at birth had reduced systolic function compared to children without but did not have progression of LV dysfunction or extent of trabeculations. In first-degree relatives to children with LVNC, 30% fulfilled criteria.

To form fully functional four-chambered structure, mammalian heart development undergoes a transient finger-shaped trabeculae, crucial for efficient contraction and exchange for gas and nutrient. Although its developmental origin and direct relevance to congenital heart disease has been studied extensively, the time-resolved cellular mechanism underlying hypotrabeculation remains elusive. Here, we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h. Compared to control, hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms: both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration. Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner. Thus, our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.

UNASSIGNED: Functional assessment of compact myocardium and hypertrabeculations in left ventricular non-compaction (LVNC) is underestimated with regards to the morphological spectrum of disease. We aimed to assess whether measuring concurrently left ventricular (LV) volume, mass and ejection fraction (LVEF) with and without trabeculation inclusion on cine magnetic resonance (cineMR) could help diagnose patients with LVNC by comparison to normal individuals with an excess of myocardial trabeculations.
UNASSIGNED: This retrospective single center magnetic resonance imaging study (Bichat University Hospital) of 67 consecutive patients with echocardiographic hypertrabeculations seen at echocardiography between March 2011 and October 2018 included 30 patients with known LVNC and 16 control subjects with simple hypertrabeculations (non-compact/compact (NC/C) ratio between 1.8 and 2.2, trabeculations involving 10% to 17% of the left ventricle) using steady-state free precession (SSFP) cine sequences in the standard views. LV volumes, mass and LVEF were measured with and without trabeculation inclusion using CVI42 software. Follow-up was studied in 20 patients and 14 controls. Functional parameters were compared using Student\'s paired t-test. Pearson product moment correlation coefficients were calculated. Bland-Altman analysis determined the inter- and intra-reader functional data reproducibility.
UNASSIGNED: When excluding the trabeculations (i.e. non-compacted myocardium) from measurements, LVEF was within normal ranges both in patients and controls, while it increased by 9.8%±1.6% in LVNC and decreased by 10.9%±1.4% in controls when trabeculae were included in the endocardial contours (P<0.0001). The overall myocardial mass remained stable according to the diastolic or systolic phase in LVNC whereas it significantly decreased in controls.
UNASSIGNED: Depending whether trabeculations were included or not, LVEF measurements were significantly different between patients with LVNC and controls. These distinctive measurements might be used as an adjunctive clinical tool to help confirm the diagnosis of LVNC.

BACKGROUND: There has been an increase in the reporting of cases of left ventricular noncompaction (LVNC) cardiomyopathy in medical literature due to advances in medical imaging. Patients with LVNC may be asymptomatic or may present with arrhythmias, heart failure, thromboembolism or sudden death. LVNC is typically diagnosed by echocardiography, although there are higher-resolution cardiac imaging techniques such as cardiac magnetic resonance imaging (MRI) to make the diagnosis. The objective of the study is to report on a series of 9 cases of LVNC cardiomyopathy seen at the University College Hospital, Ibadan. Cases of LVNC seen between September 1, 2015 and July 31, 2022 in our echocardiography service  is being reported.
RESULTS: There were a total of 6 men and 3 women. Mean age at presentation was 52.89 ± 15.02 years. The most common mode of presentation was heart failure (6 patients). Hypertension was the most common comorbidity (6 patients). Three patients had an ejection fraction of less than 40% and the mean ratio of noncompacted to compacted segment at end-systole was 2.80 ± 0.48. The most common areas of trabecular localization were the LV lateral wall and the apex. Beta blockers were highly useful in the management of the patients.
CONCLUSIONS: LVNC cardiomyopathy is not uncommon in our environment and a high index of suspicion is often required.

Abnormal cardiac development is intimately associated with congenital heart disease. During development, a sponge-like network of muscle fibers in the endocardium, known as trabeculation, becomes compacted. Biomechanical forces regulate myocardial differentiation and proliferation to form trabeculation, while the molecular mechanism is still enigmatic. Biomechanical forces, including intracardiac hemodynamic flow and myocardial contractile force, activate a host of molecular signaling pathways to mediate cardiac morphogenesis. While mechanotransduction pathways to initiate ventricular trabeculation is well studied, deciphering the relative importance of hemodynamic shear vs. mechanical contractile forces to modulate the transition from trabeculation to compaction requires advanced imaging tools and genetically tractable animal models. For these reasons, the advent of 4-D multi-scale light-sheet imaging and complementary multiplex live imaging via micro-CT in the beating zebrafish heart and live chick embryos respectively. Thus, this review highlights the complementary animal models and advanced imaging needed to elucidate the mechanotransduction underlying cardiac ventricular development.

Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited.
We screened the complete exome sequence database of the Pediatrics Cardiac Genomics Consortium and identified a cohort with a de novo CHD4 (chromodomain helicase DNA-binding protein 4) proband, CHD4M202I, with congenital heart defects. We engineered a humanized mouse model of CHD4M202I (mouse CHD4M195I). Histological analysis, immunohistochemistry, flow cytometry, transmission electron microscopy, and echocardiography were used to analyze cardiac anatomy and function. Ex vivo culture, immunopurification coupled with mass spectrometry, transcriptional profiling, and chromatin immunoprecipitation were performed to deduce the mechanism of CHD4M195I-mediated ventricular wall defects.
CHD4M195I/M195I mice developed biventricular hypertrabeculation and noncompaction and died at birth. Proliferation of cardiomyocytes was significantly increased in CHD4M195I hearts, and the excessive trabeculation was associated with accumulation of ECM (extracellular matrix) proteins and a reduction of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1), an ECM protease. We rescued the hyperproliferation and hypertrabeculation defects in CHD4M195I hearts by administration of ADAMTS1. Mechanistically, the CHD4M195I protein showed augmented affinity to endocardial BRG1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4). This enhanced affinity resulted in the failure of derepression of Adamts1 transcription such that ADAMTS1-mediated trabeculation termination was impaired.
Our study reveals how a single mutation in the chromatin remodeler CHD4, in mice or humans, modulates ventricular chamber maturation and that cardiac defects associated with the missense mutation CHD4M195I can be attenuated by the administration of ADAMTS1.

UNASSIGNED: Right ventricle (RV) mass is an imaging biomarker of mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR). Some methods of RV mass measurement on cardiac MRI (CMR) exclude RV trabeculation. This study assessed the reproducibility of measurement methods and evaluated whether the inclusion of trabeculation in RV mass affects diagnostic accuracy in suspected pulmonary hypertension (PH).
UNASSIGNED: Two populations were enrolled prospectively. (i) A total of 144 patients with suspected PH who underwent CMR followed by right heart catheterization (RHC). Total RV mass (including trabeculation) and compacted RV mass (excluding trabeculation) were measured on the end-diastolic CMR images using both semi-automated pixel-intensity-based thresholding and manual contouring techniques. (ii) A total of 15 healthy volunteers and 15 patients with known PH. Interobserver agreement and scan-scan reproducibility were evaluated for RV mass measurements using the semi-automated thresholding and manual contouring techniques.
UNASSIGNED: Total RV mass correlated more strongly with MPAP and PVR (r = 0.59 and 0.63) than compacted RV mass (r = 0.25 and 0.38). Using a diagnostic threshold of MPAP ≥ 25 mmHg, ROC analysis showed better performance for total RV mass (AUC 0.77 and 0.81) compared to compacted RV mass (AUC 0.61 and 0.66) when both parameters were indexed for LV mass. Semi-automated thresholding was twice as fast as manual contouring (p < 0.001).
UNASSIGNED: Using a semi-automated thresholding technique, inclusion of trabecular mass and indexing RV mass for LV mass (ventricular mass index), improves the diagnostic accuracy of CMR measurements in suspected PH.

OBJECTIVE: To compare clinical findings and urodynamic parameters according to trabeculation grade and analyze their correlations with trabeculation severity in neurogenic bladder caused by suprasacral spinal cord injury (SCI).
METHODS: A retrospective chart review was performed of neurogenic bladder caused by SCI. Bladder trabeculation grade was compared with SCI-related clinical parameters and bladder-related urodynamic parameters.
RESULTS: In SCI patients, factors such as disease duration, bladder capacity, detrusor pressure, peak detrusor pressure values, and compliance were significantly different between different grades of bladder trabeculation, while neurological level of injury, completeness, and detrusor sphincter dyssynergia had no clear relationship with bladder trabeculation grade. In the correlation analysis, vesicoureteral reflux was moderately correlated with trabeculation grade (correlation coefficient 0.433), while the correlation coefficients of disease duration, involuntary detrusor contraction, and bladder filling volume were between 0.3 and 0.4.
CONCLUSIONS: Bladder trabeculation with suprasacral-type neurogenic bladder was graded. Although disease duration was positively correlated with bladder trabeculation grade, differences in the neurological level of injury or American Spinal Injury Association Impairment Scale score were not observed. Bladder volume, peak detrusor pressure, compliance, reflex volume, and vesicoureteral reflux also showed significant differences according to trabeculation grade. Vesicoureteral reflux was moderately correlated with trabeculation grade.

Right ventricular (RV) involvement in left ventricular (LV) non-compaction (LVNC) remains unknown. We aimed to describe the RV volumetric, functional, and strain characteristics and clinical features of patients with LVNC phenotype and good LV ejection fraction (EF) using cardiac magnetic resonance to characterize RV trabeculation in LVNC and to study the relationships of RV and LV trabeculation with RV volume and function. This retrospective study included 100 Caucasian patients with LVNC phenotype and good LV-EF and 100 age- and sex-matched healthy controls. Patients were further divided into two subgroups according to RV indexed trabecular mass [RV-TMi; patients with RV hypertrabeculation (RV-HT) vs. patients with normal RV trabeculation (RV-NT)]. We measured the LV and RV volumetric, functional, and TMi values using threshold-based postprocessing software and the RV and LV strain values using feature tracking and collected the patients\' LVNC-related clinical features. Patients had higher RV volumes, lower RV-EF, and worse RV strain values than controls. A total of 22% of patients had RV-TMi values above the reference range; furthermore, RV-HT patients had higher RV and LV volumes, lower RV- and LV-EF, and worse RV strain values than RV-NT patients. We identified a strong positive correlation between RV- and LV-TMi and between RV-TMi and RV volumes and a significant inverse relationship of both RV- and LV-TMi with RV function. The prevalence of LVNC-related clinical features was similar in the RV-HT and RV-NT groups. These results suggest that some patients with LVNC phenotype might have RV non-compaction with subclinical RV dysfunction and without more severe clinical features.