Noncompaction Of Ventricular Myocardium In Patients With Clinical Features, Imaging Characteristics And Candidate Gene Mutation Screening

Abstract1Left ventricular noncompaction:clinical features and prognosisLeft ventricular noncompaction (LVNC) is a distinct cardiomyopathy. It is characterized by a thickened bilayered left ventricular wall consisting of a thick endocardial layer with prominent intertrabecular recesses with a thin, compact epicardial layer. Patients with LVNC can develop symptomatic congestive heart failure, various arrhythmias or systemic embolic events. Initially the noncompaction of the left ventricle was described in the pediatrics population with poor prognosis, but recent reports draw a different conclusion.[Objective] The purpose of this study was to identify the clinical characteristics and outcomes in patients with LVNC.We retrospectively reviewed112patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January2006to August2010and analyzed the clinical manifestations and outcomes of them. Cox regression analysis was used to find the predictors of the cardiac events.[Result] The common presentation of112patients involves heart failure symptoms, arrhythmias, chest pain and syncope. Seventeen patients are familial cases and95are sporadic cases. The ECG was abnormal in109cases (97%). Arrhythmias of those cases comprise atrial fibrillation (21%), Wolff-Parkinson-White syndrome (4.5%), complete atrioventricular block(8%), non-sustained ventricular tachycardia(31%), sustained ventricular tachycardia (9%)and ventricular fibrillation (5%). Four patients had hypertrophic cardiomyopathy and three patients had restrictive cardiomyopathy. Of these patients, three received an automatic implantable cardioverter defibrillator (ICD) for secondary prevention, three received cardiac resynchronization therapy. A CRT defibrillator (CRT-D) was implanted in one patients with VT/VF and heart failure. Left ventricular systolic function was depressed in103patients (92%). Fifteen patients(13.39%) received heart transplantation and fifteen died during the follow-up period. The age at initial presentation was a prognostic factor of mortality in LVNC. In multivariate COX analysis, BMI(Hazard Ratio=0.841,95%CI0.731-0.967, P=0.015), stage of heart failure(Hazard Ratio=3.720,95%CI1.225-11.299, P=0.020) and serum creatinine(LogCr, Hazard Ratio=15.829,95%CI1.570-159.582, P=0.019) are independent prognostic factors of cardiac events.[Conclusion] The clinical presentations of LVNC varies widely, most of the patients developed heart failure. LVNC can co-exist with restrictive and hypertrophic cardiomyopathy. A better prognosis was associated with increased age of onset and BMI, but serum creatinine and stage of heart failure were positively related to a poorer prognosis. However, it seems prognosis was much better than initially reported. Abstract2Left ventricular noncompaction:Imaging findingsLeft ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a thin, compacted epicardial layer and an extremely thick endocardial layer with prominent trabeculation and deep recesses, consequent to the arrest of the normal myocardium embryogenesis. Echocardiography is considered to be the gold standard method for diagnosing LVNC and three different diagnostic criteria have to date been published, although there is no universally accepted definition of LVNC at present. Some novel diagnostic criteria have been proposed but have not got agreement widely.To analyze echocardiography characteristics and cardiac magnetic resonance imaging (CMR) characteristics in patients with LVNC and improve the criteria in diagnosis of LVNC.[Methods] We collected a cohort of patients with LVNC from January2009to August2010.38transthoracic echocardiograms,52magnetic resonance images and19images of Myocardial perfusion(SPECT) and18F-FDG myocardial metabolism imaging (PET/CT) were analyzed by at least2blinded reviewers using17-segment model respectively.Of38patients, ratio of thick noncompacted layer(N) to thin compacted(C)were measured in end-systole and end-end-diastole respectively. The segments numbers of N/C>2that measured in end-systole and end-end-diastole were nearly consistent(Kappa=0.9414(95%CI0.9139-0.9688)). LVEF measured in echocardiography and NT-proBNP showed no correlation with N/C ratio, thickness of compacted layer(C) and the numbers of involved segments. According to the echocardiography criteria, CMR has got agreement with echocardiography only in71%segments. The compacted layer thickness of noncompacted segments are significantly thinner than the adjacent normal segments. C/Cn<0.6and C/Cn<0.6might be considered as the secondary criteria of LVNC. C value is negatively related to N/C ratio(P<0.0001). Myocardial perfusion at rest and18F-FDG myocardial metabolism imaging showed ischemia myocardium in some segments. The impairment of perfusion and metabolism of LVNC is firstly reported by our study. The compacted layer thickness of noncompacted segments should be considered in the diagnosis of LVNC. Ischemia myocardium in LVNC might due to the dysfunction of microcirculation of coronary artery and be the basis of heart failure and ventricular arrhythmias. Abstract3Mutations in MYH7, ACTC1and TAZ/G4.5in Left Ventricular NoncompactionLeft ventricular noncompaction(LVNC), also known as noncompaction or spongy myocardium, is a cardiac abnormality of unknown etiology. The genetic basis of this cardiomyopathy is still largely unresolved. Similar to hypertrophic and dilated cardiomyopathy, LVNC is genetically heterogeneous and was recently associated with mutations in numerous genes including MYH7, ACTC and TAZ/G4.5.To screen the disease-causing gene mutation in Chinese patients with Left ventricular noncompaction.[Methods] Mutational analysis in a cohort of57unrelated probands with left ventricular noncompaction and no other congenital heart anomalies was performed by direct DNA sequencing of MYH7, ACTC and TAZ/G4.5.Nine variants, including of4single nucleotide polymorphism (SNPs), were found. Five heterozygous mutations were identified in4of57probands in gene encoding β-myosin heavy chain (MYH7), no mutation was found in ACTC and TAZ/G4.5. Five distinct mutations(c.1699C>T,c.4806C>T,c.4872G>A,c.5329G>A, c.5421C>T) were all novel. c.1699C>T(Arg567Cys) and c.5329G>A (Ala1777Thr) are missense mutations, the others are synonymous mutations. One missense mutation, c.1699C>T, was identified in exon16of the MYH7gene in one case of LVNC, which resulted a arginine (Arg) to cysteine(Cys) exchange at amino acid residue567. The other missense mutation, c.5329G>A, was identified in exon37of the MYH7gene in one case of LVNC, which resulted an alanine (Ala) to threonine (Thr) exchange at amino acid residue1777. No mutation was found in ACTC1and TAZ/G4.5.[Conclusion] We conclude that left ventricular noncompaction might be triggered by sarcomere protein gene defects, such as MYH7. It is possible that a shared molecular etiology of LVNC and the other cardiomyopathic phenotypes.