New Paradigm Of Familial Non Compaction Associated With Hypertrophic Cardiomyopathy-an Echocardiographic Exploration

Background-Noncompaction of the ventricular myocardium is a cardiomyopathy thought to becaused by arrest of normal embryogenesis of the endocardium and myocardium. The leftventricle is characterized by multiple trabeculations with deep intertrabecular recesses. In2006,the American Heart Association classified this entity as a primary cardiomyopathy of geneticorigin. This abnormality is often associated with other congenital cardiac defects, but it is alsoseen in the absence of other cardiac anomalies. Isolated noncompaction of the ventricularmyocardium, is characterized by persistent embryonic myocardial morphology found in theabsence of other cardiac anomalies to explain the abnormal development. Both familial andsporadic forms of noncompaction have been described. Clinical manifestations are highlyvariable, ranging from no symptoms to disabling congestive heart failure, arrhythmias, andsystemic thromboemboli. Echocardiography has been the diagnostic procedure of choice, but thecorrect diagnosis is often missed or delayed because of lack of knowledge about this uncommondisease and its similarity to other diseases of the myocardium and endocardium.Hypertrophic cardiomyopathy (HCM) is a complex genetically determined myocardial diseasewith a heterogeneous spectrum. It is the most commonly inherited cardiac disease in thepopulation, occurring in1:500. There have been studies reporting HCM as the most commoncause of sudden cardiac death in those aged less than30years and an important predispositionfor heart failure, arrhythmias irrespective of age. HCM is characterized by a hypertrophic leftventricle, without ventricular dilation and in the absence of any other cardiac or systemic diseasewhich may have been the cause for the wall thickening. Hypertrophic cardiomyopathy isinherited as a mendelian autosomal dominant trait and caused by mutations in any1of10genes,each encoding proteins of the cardiac sarcomere. Clinical diagnosis is by2-dimensionalechocardiographic identification of otherwise unexplained left ventricular wall thickening in the presence of a non dilated cavity in the absence of another cardiac or systemic disease (eg,hypertension or aortic stenosis) capable of producing the magnitude of hypertrophy evident.Recently, NCC and HCM have been linked together by the same disease causing genes. Thegenetic studies about alpha-cardiac actin gene (ACTC), beta myosin heavy chain gene (MYH7),cardiac troponin T and other sarcomeric gene mutations provide the link between thesecardiomyopathies, revealing them as overlapping entities. Previous reports about patients sharingboth NCC and HCM phenotypes suggest a strong genetic association. This study involved a fourgeneration Chinese family demonstrating the coexistence of NCC and HCM in the kindreds. Anechocardiographic exploration was performed to evaluate its utility as the first diagnosticmodality of choice in NCC and HCM.Method-A four generation chinese family, comprising of30members was selected (21male,9female) amongst which27underwent familial screening.7kindred were recruited in our hospitalwho were all examined by echocardiography, while some also performed ECG, MRI, leftventricular and coronary artery angiography. Echocardiographic and MRI findings were furthercompared.Results-Features of LVNC associated with HCM were identified in the proband, aged48years,who presented with congestive heart failure. Familial screening by means of UCG/MRI revealedthat11out of the27members suffered from LVNC, HCM or both. The distribution was asfollows:6HCM&LVNC,4HCM and1LVNC. Kindred with cardiomyopathies, examined inour hospital numbered to7(3adult males,2adult females and2children). Amongst them,5were symptomatic and rest asymptomatic. The diagnoses were as follows:2HOCM&LVNC,4HCM&LVNC, and1isolated LVNC. The locations of hypertrophic lesions included IVS,anterior and LV inferior wall, with thickness of1.6-2.0cm in adult. In addition, the locations ofLVNC lesions included anterior, lateral wall, anteroseptum and apex, with the ratio of N/C2.5-4.4. Echocardiography also demonstrated LA dilatation and a decrease in diastolic function inmost of the subjects. As UCG and MRI findings showed similar results, a good correlation inlocation and quantification of the lesion between these two imaging modalities was established.ECG abnormalities were detected in most of the recruits. Conclusion-LVNC and HCM coexists in this family, thereby supporting the basis of hereditarydiseases with shared genetic defects. Phenotypes in this family show similarity but vary in termsof age, clinical manifestations and imaging findings. UCG and MRI findings concerning thesediseases were in agreement. Echocardiography is a sensitive and useful as the initial diagnostictool for these two diseases. Myocardial contrast echocardiography remains a beneficial modalityin order to improve echocardiographic imaging in diagnosis of cardiomyopathies.