Study On Early Diagnosis Of Sarcomere Gene Mutation Carriers With Hypertrophic Cardiomyopathy Using Three-dimensional Speckle Tracking Technology Combined With Electrocardiogra

Part I Assessment of left ventricular dysfunction of sarcomere mutation carriers in hypertrophic cardiomyopathy with three-dimensional speckle tracking imaging combined with conventional echocardiographyObjective To explore the value of three-dimensional speckle tracking imaging(3D-STI)and conventional echocardiography in evaluating left ventricular function characteristics of sarcomere mutation carriers in hypertrophic cardiomyopathy.Methods Totally 91 subjects with sarcomere mutations in family HCM but without left ventricular hypertrophy(G+/P-),and 100 normal family members with gender and age matched as the control group(G-/P-)were enrolled from the center of hypertrophic cardiomyopathy of Xijing hospital affiliated to the air force military medical university from February 2013 to April 2017.They all received the comprehensive evaluation of 3D-STI and conventional echocardiography.Results Compared with the G-/P-group,the G+/P-group had larger left atrial diameter(LAD),longer left ventricular isovolumic relaxation time(IVRT),reduced mitral annular systolic velocity(e’),elevated E/e’ ratio,as well as impaired left ventricular global longitudinal and radial strain(GLS and GRS).Moreover,the GLS and IVRT showed the best diagnostic performance of those with sarcomere mutations.Conclusions In HCM family members,the sarcomere mutations carriers without left ventricular hypertrophy show impaired left ventricular diastolic function,reduced longitudinal and radial systolic function.Moreover,the GLS and IVRT show the best diagnostic performance of those with sarcomere mutations.Part II The early diagnostic value of ECG for sarcomere mutation carriers with family hypertrophic cardiomyopathyObjective To explore the value of ECG in spotting sarcomere mutation carriers with family hypertrophic cardiomyopathy(FHCM)at an early phase.Methods We selected 60 FHCM patient’ relatives carrying sarcomere mutations but not complicating left ventricular hypertrophy as gene positive/phenotype negative group(G+/P-group)while 73 FHCM patients’ relatives without carrying sarcomere mutation or left ventricular hypertrophy were considered as gene negative/phenotype negative group(G-/P-group or control group).The G+/P-group and control group were well matched in sex and age.Conventional 12-lead ECG indexes were analyzed between the two groups.The efficacy of ECG parameters in diagnosing FHCM sarcomere mutation carriers was evaluated by the receiver operating characteristic curve(ROC)analysis.Results(1)The QRS duration of lead I,a VR and a VF,and R-wave amplitude in lead V1 and V2 in G+/P-group were significantly higher than those in control group(P<0.05);in G+/P-group,R-wave amplitude in lead V4-V6 were significantly lower if compared with the control group(P<0.05).(2)The proportion of T-wave changes(including T-wave flatness,inversion and bi-direction)in G+/P-group was significantly higher than that in the control group(28.3%vs19.2%,P<0.05).There was no statistically significant difference of Sokolow-Lyon voltage index(SV1+RV5 or RV6≥3.5m V),abnormal Q-wave and the proportion of fragmented QRS wave between the two groups(P>0.05).Conclusion Among the FHCM patients carrying sarcomere mutation,ECG changes are manifested by the prolongation of QRS duration,amplitude variation of R-wave in chest leads and T wave changes at an early phase,which are valuable for making early diagnosis for these patients.Part III The early diagnostic value of progression for sarcomere mutation carriers in family hypertrophic cardiomyopathy with three-dimensional speckle tracking imaging combined with ECGObjective To predict evolution of sarcomere mutation carriers in hypertrophic cardiomyopathy by using three-dimensional speckle tracking imaging combined with electrocardiogram.Methods Following up total 37 subjects with sarcomere mutations in HCM family without left ventricular hypertrophy(G+/P-)for a period of time,end point was considered as left ventricular hypertrophy.Finally,there were 5 G+/P-individuals developed into HCM as G+/P+ group and 32 remains as G+/P-.They were enrolled in the center of hypertrophic cardiomyopathy of Xijing Hospital affiliated to the Air Force Military Medical University from February 2013 to April 2017.They all received the comprehensive evaluation of 3D-STI and routine echocardiography and electrocardiogram.This study assessed the diagnostic efficacy of multiple parameters for sarcomere mutation carriers by the difference between G+/P+ group and G+/P-group at the time when they were first enrolled(before follow-up).Results Compared with the G+/P-group,the G+/P+ group had more thickened maximum left ventricular wall thickness(MLVWT),(left ventricular mass index)LVMI,larger left atrial diameter(LAD),left atrial volume index(LAVI)and the left ventricular outflow tract gradient(LVOT-PG),longer P wave duration,increased abnormal ST-T frequency,as well as impaired left ventricular global area,longitudinal and radial strain(GAS,GLS and GRS).Moreover,the LVOT-PG,MLVWT,LAVI,GLS,and P wave duration showed the optimal diagnostic performance among those developed sarcomere mutations carriers.Conclusions In HCM family members,the sarcomere mutations carriers without left ventricular hypertrophy showed the thickened left ventricular wall,impaired left ventricular systolic function,reduced area,longitudinal and radial systolic function as well as increased left atrial diameter(LAD)in the progress of developing into HCM.Moreover,the LVOT-PG,MLVWT,LAVI,GLS,and P wave duration showed the optimal diagnostic efficacy among those developed sarcomere mutations carriers.