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.

[Saw tooth cardiomyopathy: How to better diagnose?] / Saw tooth cardiomyopathy : comment mieux faire le diagnostic ?

With the increasing use of cardiac MRI, several cases were described as "sawtooth cardiomyopathy" or "tiger heart". The pathological aspects of these rare forms of myocardial dysplasia, frequently assimilated to non-compaction of the left ventricle, and its prognostic implications remain unclear. We present a case of "sawtooth cardiomyopathy" in a patient with a transient ischemic attack. This article aims to determine, with the other clinical cases in the literature, the MRI and echocardiography criteria for the diagnosis of this cardiomyopathy. Sawtooth cardiomyopathy is probably under diagnosed and deserves to be better known.

[Non-compaction and restrictive cardiomyopathy in pediatrics: Two types of myocardial diseases that are important to recognize]. / Miocardiopatía no compactada y restrictiva en pediatría: Dos tipos de enfermedades del miocardio que son importantes saber reconocer.

Left ventricular non-compaction (LVNC) and restrictive cardiomyopathies (RCM) are rare diseases with high morbidity and mortality in the pediatric age group, particularly the restrictive. They can be diagnosed at any age even in fetal life, in isolation or association with other cardiomyopathies or congenital heart disease. The causes may be genetic, neuromuscular, metabolic, storage, or idiopathic disorders. The main morphological characteristic of LVNC is the presence of a non-compact myocar dium with numerous prominent trabeculations and deep recesses, which may results in myocardial dysfunction, malignant arrhythmias and thromboembolism. On the other hand, in RCM there is an abnormal myocardial stiffness, which generates a restrictive ventricular filling and atrial dilatation secondary. Clinically it manifested by severe diastolic dysfunction, pulmonary hypertension, arrhyth mias and sudden death. For both cardiomyopathies, the Doppler color echocardiography, electro cardiography and Holter monitoring of arrhythmias are the gold standard for diagnosis and follow up. Cardiac resonance adds information on functional assessment and quantification of myocardial fibrosis. The therapy is oriented to improve symptoms and quality of life. Patients with severe forms of LVNC and RCM may require extracorporeal ventricular support and cardiac transplantation, even in early stages of the disease. The pediatrician plays an important role in the early recognition of these pathologies for timing to referral as well as in the follow-up and screening for complications. The objective of this review is to update the clinical, genetic, diagnostic, therapeutic issues and prognostic of the LVNC and RCM.

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.

Taquicardia ventricular idiopática em portador de miocárdio não compactado / Idiopathic ventricular tachycardia in patient with noncompacted myocardium

Relatamos o caso de paciente do sexo masculino, com 23 anos de idade, portador de miocárdio não compactado e taquicardia ventricular monomórfica sustentada. O paciente foi submetido a implante de cardiodesfibrilador implantável após diagnóstico confirmado por meio de ressonância nuclear magnética cardíaca e mantido em tratamento clínico com medicação antiarrítmica, sem recorrência de arritmia ventricular no acompanhamento ambulatorial

We report the case of a 23-year-old male patient with noncompacted myocardium and sustained monomorphic ventricular tachycardia. The patient was submitted to mplantable cardioverter defibrillator after diagnosis confirmed by cardiac magnetic resonance imaging and was kept on clinical treatment with antiarrhythmic medication without the recurrence of ventricular arrhythmia in the outpatient follow-up

Cardiomyopathies Due to Left Ventricular Noncompaction, Mitochondrial and Storage Diseases, and Inborn Errors of Metabolism.

The normal function of the human myocardium requires the proper generation and utilization of energy and relies on a series of complex metabolic processes to achieve this normal function. When metabolic processes fail to work properly or effectively, heart muscle dysfunction can occur with or without accompanying functional abnormalities of other organ systems, particularly skeletal muscle. These metabolic derangements can result in structural, functional, and infiltrative deficiencies of the heart muscle. Mitochondrial and enzyme defects predominate as disease-related etiologies. In this review, left ventricular noncompaction cardiomyopathy, which is often caused by mutations in sarcomere and cytoskeletal proteins and is also associated with metabolic abnormalities, is discussed. In addition, cardiomyopathies resulting from mitochondrial dysfunction, metabolic abnormalities, storage diseases, and inborn errors of metabolism are described.

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)

Noncompaction of the Ventricular Myocardium and Polycystic Kidney Disease: A Case Report.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions.

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 Diagnosis and Management Relevant to Pre-participation Screening of Athletes.

Left ventricular noncompaction (LVNC) has been extensively studied over the last years, and an increasing number of cases have been reported worldwide, with a large proportion comprising young and asymptomatic subjects, including athletes. The current epidemic of LVNC is likely the consequence of several causes, that is, the increased awareness of the disease and the refined cardiovascular imaging techniques. The current diagnostic methods, based uniquely on definition of morphologic findings, do not always resolve the overlap of a physiological myocardial architecture comprising a prominent trabecular pattern from a mild phenotypic expression of the real disease. Appropriate criteria for identification and management of LVNC in athletes have, therefore, become a novel challenge for cardiologists and sport physicians, who are required to solve the question of diagnosis and appropriate management in the setting of pre-participation cardiovascular screening. Indeed, although it is important to timely identify a true myocardial disease, to reduce the burden of adverse cardiac event in a young athlete, in contrast, a misdiagnosis of LVNC may lead to unwarranted restriction of the athlete lifestyle, with detrimental psychological, social, and economic consequences. This review report has been planned, therefore, to help physicians in diagnosing and managing athletes presenting with a morphologic pattern suggestive of LVNC with specific focus on criteria for advising sport participation.

[Noncompaction cardiomyopathy]. / "Non-compaction"-Kardiomyopathie.

Noncompaction cardiomyopathy (NCCM) is a genetic myocardial disorder, which is characterized by a two-layered ventricle wall with a thin compact outer layer and a noncompacted inner layer, with prominent trabeculations and deep intratrabecular recesses communicating with the ventricle cavity without any contact to the coronary system. Before the initial description as isolated left ventricle cardiomyopathy (ILVCN) in 1984 by Engberding and Bender, the morphological characteristics had been described only in association with other congenital cardiac disorders, such as atresia of the semilunar valves. The disease usually involves the myocardium of the left ventricle but involvement of the right ventricular has recently been shown. Due to delayed diagnosis and therapy, in advanced stages NCCM can result in heart failure. Life-threatening complications, such as malignant arrhythmia with sudden cardiac death and embolic events have been observed in patients with NCCM. A multimodal investigation including echocardiography and cardiac magnet resonance tomography (CMR) as well as a focused analysis of symptoms can allow a valid diagnosis.

Não Compactação do Ventrículo Esquerdo no Adulto: Experiência de umaClínica de Insuficiência Cardíaca / Left Ventricular Noncompaction in Adulthood: Heart Failure Clinic Experience

Fundamentos: A não compactação do ventrículo esquerdo (NCVE) é um tipo distinto de cardiomiopatia, queapresenta várias características específicas. O curso natural desta entidade não é totalmente conhecido.Objetivos: Definir as características clínicas, complicações e sobrevida de pacientes com NCVE, acompanhadosem clínica de insuficiência cardíaca (IC).Métodos: Estudo retrospectivo que incluiu pacientes com NCVE, tratados em clínica de IC do Hospital São João, na cidade do Porto, Portugal, de janeiro de 2006 a fevereiro de 2014. Os dados demográficos, sintomas de IC e fração de ejeção no início do tratamento, o curso da NCVE (alterações da classe funcional), efeitos colaterais esobrevivência foram registrados a partir dos prontuários. Resultados: Foram incluídos 10 pacientes, 6 do sexo masculino, com mediana de 63 anos de idade. Nove apresentavam sintomas de IC e começaram medicação modificadora de prognóstico. Todos tinham fração deejeção do ventrículo esquerdo <45%. Um paciente não iniciou hipocoagulação oral; 7 apresentaram algum grau de recuperação de sintomas de IC; 3 foram hospitalizados com exacerbações de IC; 1 teve acidente vascular encefálico cardioembólico; e 1 paciente foi submetido a transplante de coração.Conclusões: Os pacientes com NCVE apresentaram comorbidades semelhantes às da população geral da sua faixa etária, exceto o aparente aumento da prevalência de FA. Estes pacientes responderam bem à terapêutica para a IC com benefício clínico. Houve poucas complicações, a maioria permaneceu clinicamente estável, sem qualquer hospitalizaçãoe com baixa taxa de mortalidade. Contudo, trata-se de um pequeno grupo de pacientes com tempo de seguimento curto.

Background: Left ventricular noncompaction (LVNC) is a distinct type of cardiomyopathy that presents several specific characteristics. The natural course of this condition is not totally known. Objectives: To define the clinical characteristics, complications and survival of patients with LVNC assisted in heart failure (HF) healthcare service.Methods: Retrospective study that included patients with LVNC treated in a HF healthcare service from Hospital São João, in Porto, Portugal, from January 2006 to February 2014. Demographic data, symptoms of heart failure and ejection fraction at the beginningof treatment, the course of LVNC (changes in functional class), side effects and survival were recorded from medical records. Results: The study included 10 patients, 6 males, with a median of 63 years of age. Nine had symptoms of HF and started taking medication to modify prognosis. Everyone had left ventricular ejection fraction <45%. One patient did not start oral anticoagulation; 7 had some degree of recovery symptoms of HF; 3 were hospitalized with heart failure exacerbations; 1 had cardioembolic stroke; and 1 patient underwent heart transplant.Conclusions: Patients with LVNC had similar comorbidities as the general population of their age group, except the apparent increase in the prevalence of AF. These patients responded well to therapy for IC with some clinical benefit. There were few complications, most remained clinically stable, without any hospitalization and low mortality rate. However, it is a small group ofpatients with short follow-up time.

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.

A novel MYH7 gene mutation in a fetus with left ventricular noncompaction.

Left ventricular noncompaction (LVNC) is a recently defined cardiomyopathy characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses. LVNC is rarely described in fetal life, and a small number of cases have been reported. We report the first fetal case, to our knowledge, of LVNC associated with a novel mutation in the MYH7 gene (c.1625A>C; p.Lys542Thr). This patient showed cardiomegaly on prenatal ultrasonographic examinations, with features indicating noncompaction of the myocardium apparent in the second trimester. This case highlights the importance of prenatal ultrasonography for the diagnosis of LVNC and suggests that abnormal myocardial development underlies the pathogenesis of LVNC.

Aortic valve replacement for aortic regurgitation with rare left ventricular non-compaction.

Left ventricular noncompaction cardiomyopathy is a rare type of congenital cardiomyopathy characterized by prematurely arrested compaction of the endocardial and myocardial fibers and the progressive deterioration of left ventricular contractility. This entity is a genetically heterogeneous disorder and has a wide spectrum of presentation from no symptoms to critical disabling congestive heart failure, which can appear at any age. The prognosis is therefore varied. An elderly patient with left ventricular noncompaction underwent aortic valve replacement for associated aortic regurgitation.Follow-up at two years after surgery revealed an improved clinical condition and recovered cardiac function. This is the fourth known aortic valve replacement in a patient with left ventricular noncompaction.