BACKGROUND Left ventricular noncompaction(LVNC)is a genetic cardiomyopathy.It is characterized by intensely developed trabeculae in the ventricles with deep intertrabecular lacunae.LVNC manifests as arrhythmias and he...BACKGROUND Left ventricular noncompaction(LVNC)is a genetic cardiomyopathy.It is characterized by intensely developed trabeculae in the ventricles with deep intertrabecular lacunae.LVNC manifests as arrhythmias and heart failure with a predisposition for thrombus formation.AIM To study predictors of arrhythmic,thromboembolic events and adverse outcomes(death/transplantation)in adult patients with LVNC.METHODS Adult patients with LVNC were included(n=125;mean follow-up:14 months).Electrocardiography,echocardiography,and 24-hour electrocardiography monitoring were performed.Other procedures were conducted for some patients including:Coronary angiography;cardiac magnetic resonance imaging;cardiac computed tomography;genetic testing;myocardial pathological examination;and anti-cardiac antibody level estimation.Primary endpoints were death,heart transplantation,combined endpoint(death+transplantation),and sudden cardiac death.Secondary endpoints were intracardiac thrombosis,embolic events,myocardial infarction,sustained ventricular tachycardia(VT),and implantable cardioverter-defibrillator intervention.RESULTS LVNC manifestations included non-sustained VT,thrombosis/embolism,sustained VT, and sudden cardiac death. Non-sustained VT was associated with the New York Heart Association(NYHA) chronic heart failure (CHF) class, poor R-wave progression, superimposed myocarditis, and highermortality. Thrombosis/embolism was associated with NYHA CHF class ≥ 3, right ventricular end-diastolicdiameter ≥ 3 cm, right atrium volume ≥ 67 mL, left ventricle end-diastolic diameter ≥ 6.3 cm, and velocity timeintegral ≤ 11.2 cm. Sustained VT was associated with premature ventricular contractions (PVCs), low QRS voltage,and atrioventricular block. PVCs > 500/day were predictive of defibrillator intervention. Fatal outcomes wereassociated with E wave/A wave ratio > 1.9, left ventricle ejection fraction < 35%, NYHA CHF class ≥ 3, VT, andmyocarditis.CONCLUSIONFrequent PVCs, non-sustained VT, low QRS voltage, and signs of systolic dysfunction on echocardiogram arepredictors of life-threatening events in patients with LVNC.展开更多
Contrast echocardiography with left ventricular opacification （LVO） improves the definition of endocardium in two-dimensional echocardiography （2DE）. This study was aimed to determine whether LVO offered added dia...Contrast echocardiography with left ventricular opacification （LVO） improves the definition of endocardium in two-dimensional echocardiography （2DE）. This study was aimed to determine whether LVO offered added diagnostic value in noncompaetion of left ventricular myocardium （NCVM）. A total of 85 patients （40± 20 years, 54 males） with suspected NCVM were subjected to transthoracic 2DE and LVO, and 40 healthy volunteers were examined with 2DE and assigned as control subjects. The location of NCVM, the thickness ratio of noncompacted to compacted myocardium （NCR）, and the cavity size and ejection fraction of LV were quantified. Results revealed that NCVM was mainly located in the LV medium （53.2%）, apical （46.2%） segments, and lateral wall （39.8%）. The NCR obtained through LVO was greater than that detected through 2DE （4.2 ±1.3 vs. 3.3 ±1.2, P 〈 0.001）, and higher inter-correlations and less intra- and inter-observer variabilities were determined in the former than in the latter. The NCVM detection rates were also increased from 63.5% via 2DE to 83.5% via LVO and 89.4% via 2DE combined with LVO （2DE ＋ LVO） （P = 0.0004）. The LV cavity size was greater and the LV ejection fraction （LVEF） was lower in the NCVM patients than in the control group （P 〈 0.01）. In the NCVM group, the LV cavity size was higher and the LVEF was lower in LVO than in 2DE （P 〈 0.01）. In conclusion, contrast echocardiography contributes significant sensitivity and reproducibility to routine transthoraeic echoeardiography in NCVM diagnosis. Therefore, this technique should be clinically performed to diagnose suspected NCVM.展开更多
Left ventricular noncompaction(LVNC)is a heterogeneous disorder with undlear genetic causes and an unknown mechanism.elF3a,an important member of the Eukaryotic translation initiation factor 3(elF3)family,is involved ...Left ventricular noncompaction(LVNC)is a heterogeneous disorder with undlear genetic causes and an unknown mechanism.elF3a,an important member of the Eukaryotic translation initiation factor 3(elF3)family,is involved in multiple biological processes,indluding cell prolif eration and migration during myocardial development,suggesting it could play a role in LVNC development.To investigate the association between a novel variant(C.1145 A->G)in elF3a and LVNC,and explore potential mechanisms that could lead to the development of LVNC.A novel elF3a variant,C.1145 A->G,was identified by whole-exome sequencing in a familial pedigree with LVNC.Adenovirus vectors containing wild-type elF 3a and the mutated version were constructed and co-infected into H9C2 cells.Cell proliferation,apoptosis,cell migration,and differentiation,as well as phosphorylation of ERK1/2 were stud-ied and were measured by proliferation assays,flow cytometry,real-time PCR and Westem blot,respectively.The elF3a mutation inhibited the proliferation of H9C2 cells,induced apoptosis,promoted cell migration,and inhibited the dif ferentiation of human induced plurip-otent stem cell-derived cardiomyocytes(hiPSC-CMs).The effect of the elF3a mutation may be attributed to a decrease in expression of p-ERK1/2.A novel elF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation,differentiation,acceler-ated migration.This finding may provide some insight into the mechanism involved in LVNC development.展开更多
文摘BACKGROUND Left ventricular noncompaction(LVNC)is a genetic cardiomyopathy.It is characterized by intensely developed trabeculae in the ventricles with deep intertrabecular lacunae.LVNC manifests as arrhythmias and heart failure with a predisposition for thrombus formation.AIM To study predictors of arrhythmic,thromboembolic events and adverse outcomes(death/transplantation)in adult patients with LVNC.METHODS Adult patients with LVNC were included(n=125;mean follow-up:14 months).Electrocardiography,echocardiography,and 24-hour electrocardiography monitoring were performed.Other procedures were conducted for some patients including:Coronary angiography;cardiac magnetic resonance imaging;cardiac computed tomography;genetic testing;myocardial pathological examination;and anti-cardiac antibody level estimation.Primary endpoints were death,heart transplantation,combined endpoint(death+transplantation),and sudden cardiac death.Secondary endpoints were intracardiac thrombosis,embolic events,myocardial infarction,sustained ventricular tachycardia(VT),and implantable cardioverter-defibrillator intervention.RESULTS LVNC manifestations included non-sustained VT,thrombosis/embolism,sustained VT, and sudden cardiac death. Non-sustained VT was associated with the New York Heart Association(NYHA) chronic heart failure (CHF) class, poor R-wave progression, superimposed myocarditis, and highermortality. Thrombosis/embolism was associated with NYHA CHF class ≥ 3, right ventricular end-diastolicdiameter ≥ 3 cm, right atrium volume ≥ 67 mL, left ventricle end-diastolic diameter ≥ 6.3 cm, and velocity timeintegral ≤ 11.2 cm. Sustained VT was associated with premature ventricular contractions (PVCs), low QRS voltage,and atrioventricular block. PVCs > 500/day were predictive of defibrillator intervention. Fatal outcomes wereassociated with E wave/A wave ratio > 1.9, left ventricle ejection fraction < 35%, NYHA CHF class ≥ 3, VT, andmyocarditis.CONCLUSIONFrequent PVCs, non-sustained VT, low QRS voltage, and signs of systolic dysfunction on echocardiogram arepredictors of life-threatening events in patients with LVNC.
基金We are grateful for the support of the staff of the echocardiography laboratories in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. This project was funded by the National Natural Science Foundation of China （Nos. 81401429 and 81271582）. Dr. Li Yuan was a Visiting Fellow at Oxford Echo Core Laboratory, University of Oxford, John Radcliffe Hospital and was financially supported by Oxford University Hospitals Charitable Research Fund.
文摘Contrast echocardiography with left ventricular opacification （LVO） improves the definition of endocardium in two-dimensional echocardiography （2DE）. This study was aimed to determine whether LVO offered added diagnostic value in noncompaetion of left ventricular myocardium （NCVM）. A total of 85 patients （40± 20 years, 54 males） with suspected NCVM were subjected to transthoracic 2DE and LVO, and 40 healthy volunteers were examined with 2DE and assigned as control subjects. The location of NCVM, the thickness ratio of noncompacted to compacted myocardium （NCR）, and the cavity size and ejection fraction of LV were quantified. Results revealed that NCVM was mainly located in the LV medium （53.2%）, apical （46.2%） segments, and lateral wall （39.8%）. The NCR obtained through LVO was greater than that detected through 2DE （4.2 ±1.3 vs. 3.3 ±1.2, P 〈 0.001）, and higher inter-correlations and less intra- and inter-observer variabilities were determined in the former than in the latter. The NCVM detection rates were also increased from 63.5% via 2DE to 83.5% via LVO and 89.4% via 2DE combined with LVO （2DE ＋ LVO） （P = 0.0004）. The LV cavity size was greater and the LV ejection fraction （LVEF） was lower in the NCVM patients than in the control group （P 〈 0.01）. In the NCVM group, the LV cavity size was higher and the LVEF was lower in LVO than in 2DE （P 〈 0.01）. In conclusion, contrast echocardiography contributes significant sensitivity and reproducibility to routine transthoraeic echoeardiography in NCVM diagnosis. Therefore, this technique should be clinically performed to diagnose suspected NCVM.
基金This work was supported by the National Natural Science Foundation of China[grant number:81570218].
文摘Left ventricular noncompaction(LVNC)is a heterogeneous disorder with undlear genetic causes and an unknown mechanism.elF3a,an important member of the Eukaryotic translation initiation factor 3(elF3)family,is involved in multiple biological processes,indluding cell prolif eration and migration during myocardial development,suggesting it could play a role in LVNC development.To investigate the association between a novel variant(C.1145 A->G)in elF3a and LVNC,and explore potential mechanisms that could lead to the development of LVNC.A novel elF3a variant,C.1145 A->G,was identified by whole-exome sequencing in a familial pedigree with LVNC.Adenovirus vectors containing wild-type elF 3a and the mutated version were constructed and co-infected into H9C2 cells.Cell proliferation,apoptosis,cell migration,and differentiation,as well as phosphorylation of ERK1/2 were stud-ied and were measured by proliferation assays,flow cytometry,real-time PCR and Westem blot,respectively.The elF3a mutation inhibited the proliferation of H9C2 cells,induced apoptosis,promoted cell migration,and inhibited the dif ferentiation of human induced plurip-otent stem cell-derived cardiomyocytes(hiPSC-CMs).The effect of the elF3a mutation may be attributed to a decrease in expression of p-ERK1/2.A novel elF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation,differentiation,acceler-ated migration.This finding may provide some insight into the mechanism involved in LVNC development.
