Understanding left ventricular hypertrabeculation/noncompaction: pathomorphologic findings and prognostic impact of neuromuscular comorbidities

Stöllberger, Claudia; Finsterer, Josef

doi:10.1080/14779072.2019.1561280

Cited by 20 publications

(18 citation statements)

References 143 publications

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“…Isolated LVNC is a rare phenomenon, commonly part of other cardiovascular phenotypes, such as hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, or congenital heart defects. Thus, LNVC can be classified as (i) isolated, (ii) in combination with congenital heart defects (atrial septal defect, ventricular septal defect, and tetralogy of Fallot), (iii) in combination with other types of cardiomyopathies, neuromuscular disorders, complex genetic syndromes such as Barth syndrome, Noonan syndrome, mitochondrial disorders, or (iv) as a temporary response to cardiac overload [1,2].…”

Section: Introductionmentioning

confidence: 99%

Genetic Spectrum of Left Ventricular Non-Compaction in Paediatric Patients

et al. 2020

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Introduction: Left ventricular non-compaction (LVNC) represents a genetically heterogeneous cardiomyopathy which occurs in both children and adults. Its genetic spectrum overlaps with other types of cardiomyopathy. However, LVNC phenotypes in different age groups can have distinct genetic aetiologies. The aim of the study was to decipher the genetic spectrum of LVNC presented in childhood. Patient Group and Methods: Twenty patients under the age of 18 years diagnosed with LVNC were enrolled in the study. Target sequencing and whole-exome sequencing were performed using a panel of 108 cardiomyopathy-associated genes. Pathogenic, likely pathogenic, and variants of unknown significance found in genes highly expressed in cardiomyocytes were considered as variants of interest for further analysis. Results: The median age at presentation was 8.0 (0.1–17) years, with 6 patients presenting before 1 year of age. Twelve (60%) patients demonstrated reduced ejection fraction. Right ventricular (RV) dilation was registered in 6 (30%), often in combination with reduced RV contractility (25%). Almost half (45%) of the patients demonstrated biventricular involvement already at disease presentation. For pathogenic and likely pathogenic variants, the positive genotyping rate was 45%, and these variants were found mainly in non-contractile structural sarcomeric genes (ACTN2, MYPN, and TTN) or in metabolic and signal transduction genes (BRAF and TAZ). Likely pathogenic TAZ variants were detected in all 5 patients suspected of having Barth syndrome. No pathogenic or likely pathogenic variants were found in genes encoding for sarcomeric contractile proteins, but variants of unknown significance were detected in 3 out of 20 patients (MYH6, MYH7, and MYLK2). In 4 patients, variants of unknown significance in ion-channel genes were detected. Conclusion: We detected a low burden of contractile sarcomeric variants in LVNC patients presenting below the age of 18 years, with the major number of variants residing in non-contractile structural sarcomeric genes. The identification of the variants in ion-channel and related genes not previously associated with LVNC in paediatric patients requires further examination of their functional role.

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Section: Introductionmentioning

confidence: 99%

Genetic Spectrum of Left Ventricular Non-Compaction in Paediatric Patients

et al. 2020

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“…Incidence of cardiac complications is frequent in patients with mitochondriopathy, either in isolation, or as a component of a multisystem disease (7, 11). Cardiac involvement in mitochondriopathies is heterogeneous, ranging from conduction system disease and rhythm disease, to myocardial abnormalities such hypertrophic and dilated or non-compaction cardiomyopathies (12, 13). Cardiac involvement in nuclear genes implicated in mtDNA maintenance and repair includes sinus bradycardia, ischemic heart disease, atrial arrhythmias, conduction defects, and dilated cardiomyopathy, such has been described in Twinkle-related PEO1 mutations (14).…”

Section: Discussionmentioning

confidence: 99%

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

et al. 2019

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Objectives: To report two novel DNA2 gene mutations causing early onset myopathy with cardiac involvement and late onset mitochondriopathy with rhabdomyolysis.Methods: We performed detailed clinical, muscle histopathology and molecular studies including mitochondrial gene NGS analysis in two patients (Patient 1 and 2), a mother and her son, belonging to a Mexican family, and a third sporadic French patient.Results: Patient 1 and 2 presented with an early onset myopathy associated with ptosis, velopharyngeal weakness, and cardiac involvement. Patient 3 presented rhabdomyolysis unmasking a mitochondrial disease characterized by a sensorineural hearing loss, ptosis, and lipomas. Muscle biopsies performed in all patients showed variable mitochondrial alterations. Patient 3 had multiple mtDNA deletion in his muscle. Genetic studies revealed a novel heterozygous frameshift mutation in DNA2 gene (c.2346delT p.Phe782Leufs*3) in P1 and P2, and a novel heterozygous missense mutation in DNA2 gene (c.578T>C p.Leu193Ser) in the P3.Conclusions: To date only few AD cases presenting either missense or truncating DNA2 variants have been reported. None of them presented with a cardiac involvement or rhabdomyolysis. Here we enlarge the genetic and phenotypic spectrum of DNA2-related mitochondrial disorders.

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“…29 Chronic ischaemia, probably resulted from hypertrophy or insufficient vascular supply of the trabeculations, may cause endocardial and subendocardial fibrosis. 30 Other causes of endocardial and subendocardial fibrosis could be abnormally increased focal intraventricular pressure and immaturity of endocardial cells or subendocardial cells. 30 The presence of postischaemic myocardial dysfunction is mostly associated with adverse outcomes of patients with LVNC.…”

Section: Heart Failure and Cardiomyopathiesmentioning

confidence: 99%

“…30 Other causes of endocardial and subendocardial fibrosis could be abnormally increased focal intraventricular pressure and immaturity of endocardial cells or subendocardial cells. 30 The presence of postischaemic myocardial dysfunction is mostly associated with adverse outcomes of patients with LVNC. 1 Endocardial and subendocardial fibrosis may lead to diastolic dysfunction, restrictive filling pattern of the left ventricle and consecutive heart failure.…”

Section: Heart Failure and Cardiomyopathiesmentioning

confidence: 99%

Prognostic value of plasma big endothelin-1 in left ventricular non-compaction cardiomyopathy

Fan

Zhang

et al. 2020

Heart

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ObjectiveTo determine the prognostic role of big endothelin-1 (ET-1) in left ventricular non-compaction cardiomyopathy (LVNC).MethodsWe prospectively enrolled patients whose LVNC was diagnosed by cardiac MRI and who had big ET-1 data available. Primary end point was a composite of all-cause mortality, heart transplantation, sustained ventricular tachycardia/fibrillation and implanted cardioverter defibrillator discharge. Secondary end point was cardiac death or heart transplantation.ResultsAltogether, 203 patients (median age 44 years; 70.9% male) were divided into high-level (≥0.42 pmol/L) and low-level (<0.42 pmol/L) big ET-1 groups according to the median value of plasma big ET-1 levels. Ln big ET-1 was positively associated with Ln N-terminal pro-brain natriuretic peptide, left ventricular diameter, but negatively related to age and Ln left ventricular ejection fraction. Median follow-up was 1.9 years (IQR 0.9–3.1 years). Kaplan-Meier analysis showed that, compared with patients with low levels of big ET-1, those with high levels were at greater risk for meeting both primary (p<0.001) and secondary (p<0.001) end points. The C-statistic estimation of Ln big ET-1 for predicting the primary outcome was 0.755 (95% CI 0.685 to 0.824, p<0.001). After adjusting for confounding factors, Ln big ET-1 was identified as an independent predictor of the composite primary outcome (HR 1.83, 95% CI 1.27 to 2.62, p=0.001) and secondary outcome (HR 1.93, 95% CI 1.32 to 2.83, p=0.001).ConclusionsPlasma big ET-1 may be a valuable index to predict the clinical adverse outcomes in patients with LVNC.

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Understanding left ventricular hypertrabeculation/noncompaction: pathomorphologic findings and prognostic impact of neuromuscular comorbidities

Cited by 20 publications

References 143 publications

Genetic Spectrum of Left Ventricular Non-Compaction in Paediatric Patients

Genetic Spectrum of Left Ventricular Non-Compaction in Paediatric Patients

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

Prognostic value of plasma big endothelin-1 in left ventricular non-compaction cardiomyopathy

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