Hypertrophic cardiomyopathy (HCM) is a common primary cardiomyopathy that is closely associated with sudden death in adolescents and athletes. The disease progression of HCM is prone to structural and functional alterations in the left atrium, leading to increased incidence of acute cerebrovascular accidents, embolism and atrial fibrillation, and a severe influence on the quality of life.

To evaluate the structural and functional changes in the left atrium of family members of familial hypertrophic cardiomyopathy (FHCM) with a positive genotype but negative phenotype by real-time three-dimensional echocardiography (RT-3DE), providing valuable references for early identification, assessment and management of family members of FHCM.

A total of 141 HCM patients and family members admitted in the General Hospital of Ningxia Medical University from October 2021 to August 2022 were recruited. Blood samples were collected for genetic testing. Subjects were divided into G+P+ group with positive genotype and positive phenotype of ventricular wall thickening (n=54), G+P- group with positive genotype and negative phenotype (n=35) and G-P- group with negative genotype and negative phenotype (n=31). Baseline characteristics of subjects were collected. Two-dimensional transthoracic echocardiography (2DE-TTE) scans of the left atrium and ventricle and RT-3DE scans of the left atrium, and their relevant parameters were collected as well. Pearson correlation analysis was performed to identify the correlation between RT-3DE parameters of the left atrium and 2DE-TTE parameters of the left ventricle in subjects of G+P- group.

Genetic testing identified 24 subjects carrying the titin (TTN) gene, 2 carrying both the TTN and tropomyosin 1 (TPM1) gene, 6 carrying the myosin binding protein C3 (MYBPC3) gene, 2 carrying the troponin I3 (TNNI3) gene, 9 carrying the myosin heavy chain 7 (MYH7) gene, 8 carrying both the MYBPC3 and TNNI3 genes, and 3 carrying both the TTN and MYH7 genes in G+P+ group. In G+P- group, 11 subjects carrying the TTN gene, 8 carrying the MYBPC3 gene, 3 carrying the TNNI3 gene, 8 carrying the MYH7 gene and 5 carrying both the MYBPC3 and TNNI3 genes. 2DE-TTE parameters were analyzed. Subjects in G+P+ group showed significantly higher left atrial diameter index (LADI), left atrial volume index (LAVI), end-diastolic interventricular septal thickness (IVST), end-diastolic left ventricular posterior wall thickness (LVPWT), left ventricular mass (LVM), left ventricular mass index (LVMI) and ratio of early diastolic flow velocity peak to annular velocities (E/e') compared with those of G-P- group and G+P- group, but significantly lower end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) (P<0.05). The peak velocity blood flow from left ventricular relaxation in early diastole (the E wave) and late diastole caused by atrial contraction (the A wave) were significantly higher in subjects of G+P+ group than those of G-P- group (P<0.05). The A wave and E/e' were significantly higher in subjects of G+P- group than those of G-P- group (P<0.05). RT-3DE parameters of the left atrium were analyzed. Subjects in G+P+ group had significantly higher maximum (LAVImax) and minimum left atrial volume indices (LAVImin), and pre-contraction volume index (LAVIpre), but significantly lower left atrial total (LATEF), passive (LAPEF) and active ejection fractions (LAAEF) compared to those of G-P- group and G+P- group (P<0.05). LATEF and LAAEF were significantly lower in G+P- group than in G-P- group (P<0.05). Pearson correlation analysis showed positive correlations of LAVImax and LAVIpre with IVST (r=0.385 and 0.399, respectively; both P<0.05), positive correlations of LAVImax and LAVImin with LVM (r=0.371 and 0.432, respectively; both P<0.05), and negative correlations of LATEF and LAAEF with LVM (r=-0.375 and -0.401, respectively; both P<0.05) in G+P- group.

RT-3DE can reflect changes in left atrial function in family members of FHCM with positive genotype and negative phenotype by measuring atrial volumes, and they may already suffer from the left atrial dysfunction even when the atrial size is normal. Changes in their left atrial volume are positively correlated with changes in left ventricular wall thickness and mass, while functional changes are negatively correlated with the LVM.

肥厚型心肌病（HCM）作为一种常见的原发性心肌病，与青少年以及运动员发生猝死密切相关，疾病进展中易使左心房结构及功能发生改变，使得急性脑血管意外、栓塞、心房颤动等发病率增加，严重影响患者的生命质量。

应用实时三维超声心动图（RT-3DE）评估家族性肥厚型心肌病（FHCM）家系成员中基因型阳性表型阴性者左心房结构与功能的变化特点，为早期识别、评估及管理FHCM家系成员提供有价值的参考。

选取2021年10月—2022年8月就诊于宁夏医科大学总医院的HCM患者及其家系成员141例为研究对象，采集血液样本行基因检测。将54例携带突变基因且心室壁肥厚者作为G+P+组，35例携带突变基因且无心室壁肥厚者作为G+P-组，31例未携带突变基因且无心室壁肥厚者作为对照组。收集研究对象一般资料。采集左心房和左心室二维超声心动图（2DE-TTE），并采集左心房RT-3DE，收集相关参数。采用Pearson相关性分析探究G+P-组左心房RT-3DE参数与左心室2DE-TTE参数的相关性。

基因检测发现G+P+组中24例携带肌联蛋白基因（TTN），2例携带TTN+原肌球蛋白1（TPM1），6例携带肌球蛋白结合蛋白C3基因（MYBPC3），2例携带心肌肌钙蛋白I基因（TNNI3），9例携带β肌球蛋白重链基因（MYH7），8例携带MYBPC3+TNNI3，3例携带TTN+MYH7。G+P-组中11例携带TTN，8例携带MYBPC3，3例携带TNNI3，8例携带MYH7，5例携带MYBPC3+TNNI3。2DE-TTE常规参数比较结果示G+P+组左心房内径指数（LADI）、左心房容积指数（LAVI）、舒张末期室间隔厚度（IVST）、舒张末期左心室后壁厚度（LVPWT）、左心室质量（LVM）、左心室质量指数（LVMI）、舒张早期血流速度峰值/左房室瓣环室间隔及侧壁峰值速度（E/e'）高于对照组与G+P-组，舒张末期左心室容积指数（EDVI）、收缩末期左心室容积指数（ESVI）低于对照组与G+P-组，E、舒张晚期血流速度峰值（A）高于对照组，G+P-组A、E/e'高于对照组（P<0.05）。左心房RT-3DE参数结果示，G+P+组左心房最大容积指数（LAVImax）、左心房最小容积指数（LAVImin）、左心房主动收缩前容积指数（LAVIpre）高于对照组与G+P-组，左心房整体射血分数（LATEF）、左心房被动射血分数（LAPEF）、左心房主动射血分数（LAAEF）低于对照组与G+P-组，G+P-组LATEF、LAAEF低于对照组（P<0.05）。Pearson相关性分析结果显示，G+P-组LAVImax、LAVIpre与IVST呈正相关（r=0.385，0.399；P<0.05），LAVImax、LAVImin与LVM呈正相关（r=0.371，0.432；P<0.05），LATEF、LAAEF与LVM呈负相关（r=-0.375，-0.401；P<0.05）。

RT-3DE可通过测量左心房容积进一步反映G+P-患者左心房功能的变化；G+P-患者在左心房大小尚正常时左心房功能已受损；G+P-患者左心房容积变化与左心室室壁厚度、质量变化具有正相关性，左心房功能变化与LVM变化具有负相关性。