Isolated Left Ventricular Apical Hypoplasia without Lamin A/C Gene Mutation

Abstract Isolated left ventricular apical hypoplasia is a rare cardiomyopathy, with a broad range of clinical presentations. Since this entity was already described in association with osteomuscular diseases, mutation in the Lamin A/C gene has been regarded as a possible cause of this disease. This study describes the case of an asymptomatic teenager with isolated left ventricular apical hypoplasia and arthrogriposis but with no mutations in the entire Lamin A/C gene.

Miocardiopatia não compactada em crianças e adolescentes: do desafio do diagnóstico ecocardiográfico ao acompanhamento clínico / Non-compacted cardiomyopathy in children and adolescents: from the challenge of echocardiographic diagnosis to clinical follow-up

Fundamentos: Miocardiopatia não compactada (MCNC) caracteriza-se por hipertrabeculações e recessos profundos no ventrículo esquerdo, com apresentação clínica heterogênea, desde pacientes assintomáticos a insuficiência cardíaca (IC), eventos tromboembólicos arritmias com risco de morte súbita. Por ser rara e não apresentar critérios diagnósticos bem definidos, sua história natural na pediatria é pouco conhecida. Este estudo descreve a apresentação e evolução clínica de pacientes portadores de MCNC. Metodologia: Estudo observacional, longitudinal, prospectivo, de pacientes pediátricos atendidos em um centro de referência em cardiologia pediátrica provenientes da região metropolitana II do Estado do Rio de Janeiro, com fenótipo de MCNC ao ecocardiograma (ECO) no período de 2 anos de acompanhamento, provenientes do Registro ChARisMa. Resultados: Analisados seis pacientes com MCNC, de 4 a 14 anos de idade, média de idade de 7,5 anos (DP: 3,93), 3 do sexo masculino (50%). Apresentando-se com IC (n=2), sopro cardíaco (n=1), arritmia cardíaca (n=1), assintomático (n=1) ou em investigação de síndrome genética (n=1). Fenótipos ao ECO: MCNC/Miocardiopatia dilatada (n=1) e MCNC/Miocardiopatia restritiva (n=1), fenótipo isolado de MCNC (n=4). A ressonância magnética cardíaca foi realizada, confirmando o diagnóstico (n=4). Os desfechos observados foram tromboembolismo, indicação de transplante cardíaco e taquicardia ventricular sustentada. Conclusões: Esta série de casos proporciona dados relevantes da MCNC pediátrica, mostrando a heterogeneidade da apresentação clínica, bem como a ocorrência de complicações potencialmente fatais. São necessários mais estudos prospectivos para que seu diagnóstico seja corretamente realizado e sua evolução clínica, resposta terapêutica e prognóstico sejam mais bem conhecidos. (AU)

Background: Non-compacted cardiomyopathy (NCCM) is characterized by hypertrabeculations and deep recesses in the left ventricle, with a heterogeneous clinical presentation, ranging from asymptomatic patients to those with heart failure (HF), thromboembolic events and arrhythmias with risk of sudden death. As it is rare and does not have well-defined diagnostic criteria, its natural history in pediatrics is poorly understood. This study describes the clinical presentation and clinical course of patients with NCCM. Methodology: Observational, longitudinal, prospective study of pediatric patients seen at a pediatric cardiology referral center from metropolitan region II in the state of Rio de Janeiro, with NCCM phenotype on echocardiogram (ECHO) during a 2-year follow-up, from the ChARisMa registry. Results: 6 patients aged 4 to 14, with NCCM, were analyzed. Mean age 7.5 years (SD: 3.93), 3 males (50%). The patients presented HF (n=2), cardiac murmur (n=1), cardiac arrhythmia (n=1), were asymptomatic (n=1) or were under investigation for a genetic syndrome (n=1). Phenotypes on ECHO: NCCM/dilated cardiomyopathy (n=1) and NCCM/restrictive cardiomyopathy (n=1), isolated phenotype of NCCM (n=4). Cardiac magnetic resonance imaging was performed and confirmed the diagnosis (n=4). The outcomes observed were thromboembolism, indication for heart transplantation, and sustained ventricular tachycardia. Conclusions:This case series provides relevant data for pediatric NCCM as it shows its heterogeneous clinical presentation and potentially fatal complications. More prospective studies are needed for an accurate diagnosis and to allow its clinical course, therapeutic response and prognosis to be better known. (AU)

Ventricular tachycardia triggered by pregnancy in left-ventricular non-compaction cardiomyopathy: a controversial indication to automated defibrillator implantation.

Left-ventricular non-compaction (LVNC) is a rare form of cardiomyopathy. Its clinical presentation is highly variable and during pregnancy is frequently associated with heart failure, embolic events, and arrhythmias. Herein we report a case of a woman with left ventricular non-compaction who had an automated defibrillator implantation for recurrent ventricular arrhythmias during pregnancy. During pregnancy and at long-term follow-up no interventions of the device were documented. In conclusion, the management of malignant arrhythmias during pregnancy is one of the concerns for patients with LVNC and requires a careful approach in third-level centers.

Cardiovascular Magnetic Resonance and Sport Cardiology: a Growing Role in Clinical Dilemmas.

Exercise training induces morphological and functional cardiovascular adaptation known as the "athlete's heart" with changes including dilatation, hypertrophy, and increased stroke volume. These changes may overlap with pathological appearances. Distinguishing athletic cardiac remodelling from cardiomyopathy is important and is a frequent medical dilemma. Cardiac magnetic resonance (CMR) has a role in clinical care as it can refine discrimination of health from a disease where ECG and echocardiography alone have left or generated uncertainty. CMR can more precisely assess cardiac structure and function as well as characterise the myocardium detecting key changes including myocardial scar and diffuse fibrosis. In this review, we will review the role of CMR in sports cardiology.

Effect of Noncompacted Myocardial Resection on Isolated Left Ventricular Noncompaction.

Isolated left ventricular noncompaction, where broad trabeculae and deep intertrabecular recesses are observed in the left ventricular myocardium resulting from an arrest in normal embryogenesis, is a rare cardiomyopathy. We present a report on isolated trabeculectomy and postoperative echocardiographic follow-up showing recovery of cardiac function for isolated left ventricular noncompaction.

The effect of contrast agents on left ventricular parameters calculated by a threshold-based software module: does it truly matter?

The acquisition of short-axis (SA) cine magnetic resonance (MR) images after the administration of contrast agent (CA) is a common, time-saving technique, but a decreased difference in the blood-myocardium contrast on these steady-state free precession (SSFP) cine scans could change the calculated parameters when using threshold-based papillary and trabecular muscle (PTM) quantification. We studied the effect of CA on the parameters calculated from pre- and post-CA SA cine images in noncompaction cardiomyopathy (NC-CMP) and healthy (H) participants using a threshold-based module. A total of 39 individuals (20 patients and 19 healthy) were included prospectively in this study. After the pre-CA SA images were acquired, i.v. gadobutrol (GA) or gadobenate dimeglumine (GD) (GA vs. GD: NC-CMP = 12 vs. 8; C = 12 vs. 7) was administered, and SA scans were repeated after two minutes. A threshold-based PTM software was used for postprocessing. Pre-CA and post-CA SA images were analyzed, and the parameters were compared in both the NC-CMP and H groups. The left ventricular volumes were significantly larger, while the left ventricular myocardial (LVmass) and trabecular mass (LVtrab) values were significantly smaller on the post-CA scans (NC-CMP: pre-CA vs. post-CA, EDV: 74.0 ± 13.6 vs. 81.1 ± 16.3 ml/m2, ESV: 25.3 ± 7.3 vs. 30.1 ± 11.2 ml/m2, LVmass-ED: 82.5 ± 17.5 vs. 75.7 ± 15.9 g/m2, LVtrab-ED: 25.0 ± 6.6 vs. 18.9 ± 4.7 g/m2; Healthy: preCA vs. post-CA, EDV: 69.7 ± 11.9 vs. 72.2 ± 10.7 ml/m2, ESV: 22.6 ± 5.7 vs. 23.9 ± 6.3 ml/m2, LVmass-ED: 71.3 ± 13.6 vs. 68.7 ± 13.9 g/m2, LVtrab-ED: 19.4 ± 2.6 vs. 16.2 ± 3.0 g/m2; p < 0.05). The decreased blood-myocardium contrast difference on post-CA SSFP SA cine images leads to altered cardiac parameters when using threshold-based software for evaluation.

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

INTRODUCTION: When >3 trabeculations associated with interventricular recesses are found, this is termed 'left ventricular hypertrabeculation/noncompaction' (LVHT). Cardiac-imaging methods detect LVHT in all ages, isolated or associated with extracardiac, especially neuromuscular disorders (NMDs). Many issues about LVHT are unclear. The review gives an update about pathomorphologic findings in patients >14 years and the role of NMDs in LVHT. Areas covered: A PubMed-search for the terms "noncompaction" or "non-compaction" or "hypertrabeculation" AND "autopsy" or 'biopsy' or 'ultrastructure' or 'electron microscopy' AND 'neuromuscular' or 'myopathy' or 'neuropathy' was carried out from 1985 to July 2018. Expert commentary: Macroanatomic (n = 65), histopathologic (n = 59) and ultrastructural (n = 7) reports were found. A comparison with echocardiography was described in 45 cases. Measurements of non-compacted and compacted layer were only given from hearts investigated in short-axis cuts after formaldehyde-fixation. Endocardial, subendocardial and interstitial fibrosis were frequent findings. When LVHT-patients were systematically investigated, a NMD was found in 80%, most frequently mitochondrial disorders, Barth syndrome, zaspopathy, and myotonic dystrophy type 1. LVHT does not seem to be a special type of cardiac involvement of NMDs. NMDs affect prognosis in LVHT as well as LVHT affects prognosis in patients with Duchenne muscular dystrophy.

Atrial fibrillation in patients with inherited cardiomyopathies.

Atrial fibrillation (AF) often complicates the course of inherited cardiomyopathies and, in some cases, may be the presenting feature. Each inherited cardiomyopathy has its own peculiar pathogenetic characteristics that can contribute to the development and maintenance of AF. Atrial fibrillation may occur as a consequence of disease-specific defects, non-specific cardiac chamber changes secondary to the primary illness, or a combination thereof. The presence of AF can denote a turning point in the progression of the disease, promoting clinical deterioration and increasing morbidity and mortality. Furthermore, the management of AF can be particularly challenging in patients with inherited cardiomyopathies. In this article, we review the current information on the prevalence, pathophysiology, risk factors, and treatment of AF in three different inherited cardiomyopathies: hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy, familial dilated cardiomyopathy, and left ventricular non-compaction cardiomyopathy.

Auxiliary diagnostic potential of ventricle geometry and late gadolinium enhancement in left ventricular non-compaction; non-randomized case control study.

BACKGROUND: There are still ambiguities existing in regard to left ventricular non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry in patients with LVNC and controls. METHODS: Data on cardiac magnetic resonance imaging (CMR) studies for LVNC were reassessed from the hospital's database (3.75 years; n=1975 exams). Matching sample of controls included cases with no structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic right ventricular dysplasia or subacute myocarditis. Eccentricity of the left ventricle was measured at end diastole in the region with pronounced NC and maximal to minimal ratio (MaxMinEDDR) was calculated. RESULTS: Study included 255 patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5% (95%-CI:42.3-62.5), specificity of 80.4% (95%-CI:73.2-86.5) for LVNC, area under curve (AUC) 0.664 (95%-CI:0.603-0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity of 95.0% (95%-CI:88.7-98.4), specificity of 82.6% (95%-CI: 75.7-88.2) for LVNC, AUC 0.917 (95%-CI:0.876-0.948); p<0.001. LGE correlated with Max-Min-EDD-R (Rho=0.130; p=0.038) and there was significant difference in ROC analysis ΔAUC0.244 (95%-CI:0.175-0.314); p<0.001. LGE also correlated negatively with stroke volume and systolic function (both p<0.05, respectively). CONCLUSIONS: LGE was found to be frequently expressed in patients with LVNC, but without sufficient power to be used as a discriminative diagnostic parameter. Both LGE and eccentricity of the left ventricle were found to be relatively solid diagnostic landmarks of complex infrastructural and functional changes within the failing heart.

Variant of myocardial infarction course in the patient with left ventricular non-compaction.

Non-compacted left ventricle in adults is a rare occurrence, though it is diagnosed even more rarely. As a rule in patients with non-compacted left ventricle (LVNC) other pathologic condition is diagnosed, notably hypertrophic or dilated cardiomyopathy. The majority of LVNC cases are diagnosed in early infancy but currently there are asymptomatic cases detected by means of echocardiographic examination. Real prevalence of LVNC is unknown. According to many authors LVNC occurs in 9.2-9.5% of children with diagnosed cardiomyopathies. The majority of such children do not survive till adulthood because of progressive severe heart failure, fatal arrhythmias and thromboembolisms. This value ranges from 0.014 to 0.05% in adult population. The article presents a clinical case illustrating the stages in establishing the diagnosis of non-compacted left ventricle in a young patient with myocardial infarction and congestive heart failure. Common characteristics of non-compacted left ventricle and connective tissue dysplasia syndrome in the patient suggested etiopathogenetic relationship between these two pathologic states. The basic common characteristic feature of both non-compacted left ventricle and connective tissue dysplasia syndrome proved to be multiple abnormal chords of the left ventricle. The patient was supposed to have some coronary circulation abnormality inherited together with non-compacted left ventricle and connective tissue dysplasia syndrome. Adverse prognosis and high mortality in non-compacted left ventricle require its early recognition and differentiated approach to treatment depending on the severity of the disease and using all modern methods of treatment both conservative and surgical.

Left ventricular noncompaction and pre-excitation: an unusual finding in adults

Left ventricular noncompaction (LVNC) is a rare form of cardiomyopathy characterized by prominent left ventricular (LV) trabeculae, deep intertrabecular recesses, and the thin compacted layer. The disease is potentially associated with sudden cardiac death due to LV dysfunction and ventricular arrhythmias. The presence of accessory pathway and Wolff-Parkinson-White syndrome is particularly rare in adults. Here we describe the rare association of LVNC and ventricular pre-excitation in an 18-year-old female with neonatal hypoxic brain injury (AU)

Clinical examples of left ventricular non-compaction in adults.

INTRODUCTION: isolated left ventricular non-compaction (LVNC) is a heart disease with rather distinct morphologic and clinical manifestations. Available in the literature information about LVNC considering multiple left ventricle abnormal chords (LVAC) as one of its criterion motivated us to review the results obtained in the study of young patients with this pathology. The aim of the research was to demonstrate different clinical variants of left ventricular non-compaction course in adult patients and to clarify some pathogenetic aspects of this pathology. Materials and metods: comprehensive examination of 28 patients with multiple LVAC, 12 patients with LVNC and dilated idiopathic cardiomyopathy aged 16-36 was performed. RESULTS: according to the results of our research, 16 of 28 patients with multiple LVAC of left ventricle had ejection fraction more than 55%, in 6 patients this index range was 50-54%, in 6 it was 45-49%. Multiple LVAC were found to be associated with significantly greater clinical, phenotypic, structural and hemodynamic changes when compared both to control and solitary LVAC of any location (р<0.05). There were 12 young patients with multiple LVAC and ejection faction 22-41%. The detailed analysis of echocardiographic data in dynamics revealed other criteria of LVNC in all the patients. The data obtained suggest the relationship between pathogenetic mechanisms of heart pathology development in patients with connective tissue dysplasia syndrome and in patients with LVNС. Echocardiographic evidences of multiple LVAC designate the necessity of targeted search of left ventricular non-compacted signs and timely detection of left ventricular dilation.

Left Ventricular Noncompaction Combined With Epinephrine-Secreted Pheochromocytoma Inducing Heart Failure.

Pheochromocytomas and left ventricular noncompaction (LVNC) are both rare diseases. In this patient, the long duration of the catecholamine-secreted pheochromocytoma caused myocardial ischemia, pressure overload, and hypertrophy, resulting in the onset of heart failure (HF). The LVNC might be associated with the acute attack of HF induced by the pheochromocytoma. This is the first case reporting LVNC in combination with HF secondary to pheochromocytoma.

A novel lamin A/C gene missense mutation (445 V > E) in immunoglobulin-like fold associated with left ventricular non-compaction.

AIMS: Two LMNA mutations (R644C and R190W) have been associated with familial and sporadic left ventricular non-compaction (LVNC). However, the mechanisms underlying these associations have not been elucidated. METHODS AND RESULTS: Genomic DNA was isolated from peripheral blood leucocytes and analysed by direct sequencing. Human embryonic kidney 293 cells were transfected with either wild type or mutant LMNA and SCN5A for whole-cell patch-clamp experiment and fluorescence microscopy. Point mutation modeling for mutant LMNA was also performed. One novel LVNC-associated mutation (V445E) in ß2 sheet of immunoglobulin (Ig)-like fold was found in the proband and his father. We also found that the peak current of sodium channel was markedly reduced in mutant LMNA compared with WT while the activation, inactivation, and recovery curves were not significantly altered. The mutant lamin A/C were aggregated into multiple highlighted particles. Three ß sheets and multiple side chains in Ig-like fold were altered due to the replacement of a valine by glutamic acid. CONCLUSION: Our data associated a novel lamin A/C mutation (V445E) with a sudden death form of familial LVNC. The reduced sodium current in mutant LMNA may account for the advent of malignant ventricular arrhythmias. The altered structures of three ß sheets and side chains may partially explain the aggregation of lamin A/C protein subjacent to the nuclear envelope.

Left ventricular noncompaction in a family with lamin A/C gene mutation.

Left ventricular noncompaction is a rare type of cardiomyopathy, the genetics of which are poorly understood to date. Lamin A/C gene mutations have been associated with dilated cardiomyopathy and diseases of the conduction system, but rarely in left ventricular noncompaction cardiomyopathy. This report describes the cases of 4 family members with a lamin A/C gene mutation, 3 of whom had phenotypic expression of left ventricular noncompaction.