A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

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Assessment of regional left ventricular function in isolated left ventricular noncompaction

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(08)60094-6 ◽

2008 ◽

Vol 7 ◽

pp. 33-33

Author(s):

A VARGASZEMES ◽

L TOTH ◽

R FALUDI ◽

L PAPP ◽

T SIMOR

Keyword(s):

Left Ventricular Function ◽

Ventricular Function ◽

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Regional Left Ventricular Function ◽

Ventricular Noncompaction

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Left Ventricular Noncompaction: Evidence for a Mitochondrial Etiology

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)83847-8 ◽

1998 ◽

Vol 31 (2) ◽

pp. 30A-31A

Author(s):

D Stromberg

Keyword(s):

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction

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Faculty Opinions recommendation of Combination of whole genome sequencing, linkage, and functional studies implicates a missense mutation in titin as a cause of autosomal dominant cardiomyopathy with features of left ventricular noncompaction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726741600.793535813 ◽

2017 ◽

Author(s):

WH Wilson Tang

Keyword(s):

Whole Genome Sequencing ◽

Missense Mutation ◽

Genome Sequencing ◽

Autosomal Dominant ◽

Left Ventricular ◽

Whole Genome ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Functional Studies

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Myocardial Noncompaction

Revista de Chimie ◽

10.37358/rc.18.8.6500 ◽

2018 ◽

Vol 69 (8) ◽

pp. 2209-2212

Author(s):

Alexandru Radu Mihailovici ◽

Vlad Padureanu ◽

Carmen Valeria Albu ◽

Venera Cristina Dinescu ◽

Mihai Cristian Pirlog ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Specific Treatment ◽

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Genetic Transmission ◽

Asymptomatic Patients ◽

Increased Risk ◽

Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

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Isolated Left Ventricular Noncompaction in a Case of Sotos Syndrome: A Casual or Causal Link?

Cardiology Research and Practice ◽

10.4061/2011/824095 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Patrizia Saccucci ◽

Federica Papetti ◽

Roberta Martinoli ◽

Alessandro Dofcaci ◽

Ursula Tuderti ◽

...

Keyword(s):

Physical Examination ◽

Causal Link ◽

Left Ventricular ◽

Wall Thickening ◽

Ventricular Wall ◽

Sotos Syndrome ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Cardiac Evaluation ◽

Chromosome 5Q35

A 16-year-old boy affected by Sotos syndrome was referred to our clinic for cardiac evaluation in order to play noncompetitive sport. Physical examination was negative for major cardiac abnormalities and rest electrocardiogram detected only minor repolarization anomalies. Transthoracic echocardiography showed left ventricular wall thickening and apical trabeculations with deep intertrabecular recesses, fulfilling criteria for isolated left ventricular noncompaction (ILVNC). Some sporadic forms of ILVNC are reported to be caused by a mutation on CSX gene, mapping on chromosome 5q35. To our knowledge, this is the first report of a patient affected simultaneously by Sotos syndrome and ILVNC.

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The mitral regurgitation effects of cardiac structure and function in left ventricular noncompaction

Scientific Reports ◽

10.1038/s41598-021-84233-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qing Zou ◽

Rong Xu ◽

Xiao Li ◽

Hua-yan Xu ◽

Zhi-gang Yang ◽

...

Keyword(s):

Mitral Regurgitation ◽

Nyha Class ◽

Left Ventricular ◽

Structure And Function ◽

Left Ventricular Geometry ◽

Cardiac Structure ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Cardiac Structure And Function ◽

And Function

AbstractThis study evaluated the effects of mitral regurgitation (MR) on cardiac structure and function in left ventricular noncompaction (LVNC) patients. The clinical and cardiovascular magnetic resonance (CMR) data for 182 patients with noncompaction or hypertrabeculation from three institutes were retrospectively included. We analyzed the difference in left ventricular geometry, cardiac function between LVNC patients with and without MR. The results showed that patients with MR had a worse New York Heart Association (NYHA) class and a higher incidence of arrhythmia (P < 0.05). MR occurred in 48.2% of LVNC patients. Compared to LVNC patients without MR, the two-dimensional sphericity index, maximum/minimum end-diastolic ratio and longitudinal shortening in LVNC patients with MR were lower (P < 0.05), and the peak longitudinal strain (PLS) of the global and segmental myocardium were obviously reduced (P < 0.05). No significant difference was found in strain in LVNC patients with different degree of MR; end diastolic volume, end systolic volume, and global PLS were statistically associated with MR and NYHA class (P < 0.05), but the non-compacted to compacted myocardium ratio had no significant correlation with them. In conclusion, the presence of MR is common in LVNC patients. LVNC patients with MR feature more severe morphological and functional changes. Hypertrabeculation is not an important factor affecting structure and function at the heart failure stage.

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