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.

Left Ventricular Noncompaction: Diagnostic Approach, Prognostic Evaluation, and Management Strategies.

Left ventricular noncompaction cardiomyopathy is a heart disease with relevant potential complications including heart failure, life-threatening arrhythmias, and embolic events. In order to prevent adverse outcomes, it is crucial to appropriately recognize and manage this cardiomyopathy. In this paper, we report the main clinical presentations and imaging modalities used for diagnosis, including echocardiography and magnetic resonance imaging. We highlight the role of a comprehensive functional cardiac evaluation and the possible prognostic implications of both systolic and diastolic dysfunction. Furthermore, we summarize clinical factors and imaging findings which have prognostic significance. Finally, we discuss the main management strategies based on phenotypic expressions which are aimed at treating symptoms and preventing complications.

Left ventricular noncompaction - Risk stratification and genetic consideration.

Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by two layered structures composed of prominent trabecular meshwork and deep intertrabecular recesses. LVNC was thought to be rare; however, heightened awareness has resulted in an increased detection of the morphological features of LVNC in routine clinical practice especially in the adult population. Although LVNC was classified as an independent primary cardiomyopathy of genetic origin by the American Heart Association in 2006, its definition, diagnostic criteria and clinical implications are still being debated. Clinical manifestations are highly variable, even in the same family, ranging from no symptoms to disabling congestive heart failure, life-threatening arrhythmias, systemic thromboemboli, and sudden cardiac death. Among phenotypic subtypes of LVNC, children with isolated LVNC with normal cardiac function had the best outcomes: children with LVNC and dilated cardiomyopathy had the worst outcomes. Myocardial dysfunction or ventricular arrhythmias are predictors of mortality in adults with LVNC. LVNC, like other forms of inherited cardiomyopathy, is genetically heterogeneous and can be inherited as an autosomal dominant or X-linked recessive disorder. It has been linked to mutations in many genes, including ZASP, TAZ/G4.5, and those encoding sarcomeric, Z-disc, cytoskeleton proteins, and mitochondria. Disturbance of the NOTCH signaling pathway has been reported to be part of genetic pathway for LVNC as well. Although there are an increasing number of reports, genotype-phenotype correlations have been challenging and investigations are ongoing. Patients with mutations are more likely to have major adverse cardiovascular events, further, LV systolic dysfunction in mutation carriers makes them at high risk for cardiac events. Treatments focus on improvement in cardiac function and reduction of mechanical stress in patients with systolic dysfunction and on treatment of arrhythmia and implantation of an automatic implantable cardioverter-defibrillator for prevention of sudden death. Given that 20-40% of cases may be familial, family screening is recommended.

Potential Common Pathogenic Pathways for the Left Ventricular Noncompaction Cardiomyopathy (LVNC).

Ventricular trabeculation and compaction are two essential morphogenetic events for generating a functionally competent ventricular wall. A significant reduction in trabeculation is usually associated with hypoplastic wall and ventricular compact zone deficiencies, which commonly leads to embryonic heart failure and early embryonic lethality. In contrast, the arrest of ventricular wall compaction (noncompaction) is believed to be causative to the left ventricular noncompaction (LVNC), a genetically heterogeneous disorder and the third most common cardiomyopathy among pediatric patients. After critically reviewing recent findings from genetically engineered mouse models, we suggest a model which proposes that defects in myofibrillogenesis and polarization in trabecular cardiomyocytes underly the common pathogenic mechanism for ventricular noncompaction.

Key Questions Relating to Left Ventricular Noncompaction Cardiomyopathy: Is the Emperor Still Wearing Any Clothes?

The evidence is increasing that left ventricular noncompaction cardiomyopathy as it is currently defined does not represent a failure of compaction of pre-existing trabecular myocardium found during embryonic development to form the compact component of the ventricular walls. Neither is there evidence of which we are aware to favour the notion that the entity is a return to a phenotype seen in cold-blooded animals. It is also known that when seen in adults, the presence of excessive ventricular trabeculations does not portend a poor prognosis when the ejection fraction is normal, with the risks of complications such as arrhythmia and stroke being rare in this setting. It is also the case that images of "noncompaction" as provided from children or autopsy studies are quite different from the features observed clinically in asymptomatic adults with excessive trabeculation. Our review suggests that the presence of an excessively trabeculated left ventricular wall is not in itself a clinical entity. It is equally possible that the excessive trabeculation is no more than a bystander in the presence of additional lesions such as dilated cardiomyopathy, with the additional lesions being responsible for the reduced ejection fraction bringing a given patient to clinical attention. We, therefore, argue that the term "noncompaction cardiomyopathy" is misleading, because there is neither failure of compaction nor a cardiomyopathic process in most individuals that fulfill widely used diagnostic criteria.

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 unique foetal case of left ventricular non-compaction associated with arrhythmia, structural cardiac anomalies, and agenesis of the ductus venosus.

A 21-week gestational age foetus was diagnosed with left ventricular non-compaction, Ebstein's anomaly, sinus bradycardia, first-degree heart block, and agenesis of the ductus venosus. The prognosis was guarded given the constellation of findings, and the foetus was monitored closely. Despite a potentially poor outcome, the foetus survived. Prognosis in foetally diagnosed left ventricular non-compaction is usually poor; however, rarely, foetuses can survive postnatally.

Systemic lupus erythematosus and transient left ventricular noncompaction.

OBJECTIVES: Myocarditis is a rare but serious manifestation of patients with systemic lupus erythematosus (SLE). Left ventricular noncompaction (LVNC) is a disorder of myocardial morphogenesis frequently associated to neuromuscular diseases. Hypertrabeculation, a cardinal echocardiographic feature of LVNC, might represent a morphological expression of a number of morbidities, nevertheless. The relationship of LVNC with connective tissue disorders such as SLE is unknown. We aim to present a case of a patient with SLE who recently showed features compatible with an atypical LVNC. METHODS: To report a case of a young female with a 10-year history of SLE who developed haematological disease activity and cardiac failure. RESULTS: Ecocardiography showed hypertrabeculation/noncompaction, a very low ejection fraction and pulmonary hypertension. Clinical and echocardiographic features reverted with standard treatment for SLE activity and cardiac insufficiency. CONCLUSION: The transitory aspect of the cardiomyopathy made unlikely a "true" LVNC for this patient, but she might have presented a lupus myocarditis with "LVNC-like" features. The occurrence of hypertrabeculated myocardium in patients with SLE warrants further studies.

Left ventricular noncompaction: a cardiomyopathy with distinct characteristics and risks.

BACKGROUND: Left ventricular noncompaction (LVNC) cardiomyopathy is a heterogeneous condition that is gaining recognition as a distinct clinical entity. It is characterized by numerous, excessively prominent ventricular trabeculations with deep trabecular recesses and the formation of 2 distinct layers of myocardium. It is often unrecognized clinically for decades and poses distinct life-threatening complications. Accurate diagnosis is key to minimizing risks associated with LVNC. PURPOSE: This article will introduce clinicians to the defining criteria and diagnostic process for recognition of LVNC. Left ventricular noncompaction is an important clinical entity not easily recognized at first glance but has important clinical ramifications for treatment requiring an accurate diagnosis. CONCLUSIONS: Left ventricular noncompaction is present at birth but can remain clinically silent for decades. It is found both in isolation and as a part of other congenital cardiac, extracardiac, neuromuscular, and genetic syndromes. Left ventricular noncompaction is associated with the major complications of heart failure, tachyarrhythmias, and systemic thromboembolism. CLINICAL IMPLICATIONS: Transthoracic echocardiography will likely remain the initial screening modality, but modality limitations, questionable findings, and clinical presentations suspicious for noncompaction should be followed up promptly with cardiac magnetic resonance imaging for definitive diagnosis and treatment.

Noncompaction myocardium in association with type Ib glycogen storage disease.

Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four.