The Echocardiographic Study Of Left Ventricular Regional Diastolic Dysfunction In Hypertrophic Cardiomyopathy And Patients With Mutations In The Myosin-binding Protein C3Gene

Background:Left ventricular (LV) diastolic dysfunction has been considered a characteristic of hypertrophic cardiomyopathy (HCM). Previous studies have shown heterogeneity of myocardial function in HCM. The aim of this studyt is to assess LV regional diastolic function in patients with HCM by using single-beat real-time three-dimensional echocardiography (RT-3DE).Methods:Sixty-nine patients with HCM (LV ejection fraction≥45%) together with sixty age-and gender-matched normal controls were studied by two-dimensional echocardiography (2DE) and RT-3DE. The parameters analyzed by RT-3DE included the following:end diastolic volume(EDV), end systolic vlume(ESV), stroke(SV), ejection fraction(LVEF), end systolic/diastolic sphericity index (ESSI/EDSI), diastolic dyssynchrony index (DDI), dispersion end diastole (DISPED), including late(DDI-late) and early(DDI-early) diastole, dispersion end diastole (DISPED-late), dispersion early diastole (DISPED-early), and normalized segmental volume-time curves (17segments). Patients were divided into three groups according to Diastolic dysfunction criterion as previously described. Group1=impaired relaxation(n=23), Group2=pseudonormal filling(n=37), Group3=restrictive filling(n=9).Results:1) We compared the measurements of left ventricular function acquired by2DE and RT-3DE. A significant decrease in the EDV (93.1±17.5ml in2DE versus88.9±18.2ml in RT3DE, P<.0001) coupled with ESV (37.8±8.9ml in2DE versus33.08±9.9ml in RT3DE, P<.0001) resulted in a significant increase in the LVEF in2DE (63.2±6.8%versus59.1±6.4%, P<.0001).2) Normal subjects had relatively uniform volumetric curves for all LV segments. In HCM patients, the segmental volumetric curves were dyssynchronous. DDI and DISPED were increased with degree of diastolic dysfunction. In end diastole, DDI-late and DISPED-late were abnormal in severe diastolic dysfunction (7.95±2.75,26.76±17.19, P<.0001), while they were normal in mild diastolic dysfunction. However, in early diastole, DDI-early and DISPED-early were increased in mild (8.57±2.24,25.44±6.31, P<.0001) and moderate (9.56±4.66,35.42±14.19, P<.0001) diastolic dysfunction. And abnormal volumetric segments not only occurred in the hypertrophic regions but also in normal regions.Conclusions:Dyssynchrony in HCM was significantly increased due to regional diastolic dysfunction, especially in early diastole, suggesting that regional myocardial changes in HCM can lead to the global diastolic dysfunction. This preclinical lesion can be recognized by single-beat RT-3DE. Background:Myosin binding protein C3(MyBPC3) mutations are one of the most causes of hypertrophic cardiomyopathy(HCM). In previous studies, Mutations in MyBPC3are responsible for15-20%of cases of familial HCM and were generally associated with mild and age-related penetrance disease. Its prevalence varies between populations. However, the links between mutations in MyBPC3and changes of cardiac functions in Chinese patients with hypertrophic cardiomyopathy remain unclear. Our objectives were to determine the associated Mutations in MyBPC3in China and clinical characteristics in MyBPC3mutations in our patients using2-dimensional and real-time3-dimensional echocardiography(2DE and RT-3DE).Methods:48patients (age48±12years;31male) with HCM underwent genetic screening of MyBPC3. Following PCR amplification, direct sequencing of amplicons was performed. A variant was based on absence of the mutation in200healthy adult controls. HCM proband and families with identified MyBPC3mutations which were divided into group:genotyped HCM patients (genotype-positive G+/LVH+), mutation carriers without LVH (G+/LVH-)and matched normal control subjects (n=30)were examined with2DE including TDI and RT-3DE. TDI included:Septal and lateral TDI-derived systolic(Sa) and early(Ea) and late diastolic(Aa) mitral annular velocities, and Septal and lateral E/Ea. DDI in RT-3DE.Results:1) Nine mutations in MyBPC3were identified in7of the48index cases(15%).7HCM families with identified MyBPC3mutations which were divided into group:genotyped HCM patients (genotype-positive G+/LVH+, n=16), mutation carriers without LVH (G+/LVH-, n=22).2) Septal and lateral TDI-derived systolic(Sa) and early(Ea) and late diastolic(Aa) mitral annular velocities were significantly lower and Septal and lateral E/Ea were increased in the G+/LVH+subjects compared with the controls(13.4±3.0,8.1±3.6P<.0001). However, in G+/LVH-subjects, septal Ea were significantly lower(8.5±1.7P<.0001) and E/Ea were increased(6.6±2.4P<0.0001), while lateral TDI were no difference compared with the controls. DDI derived from3DE were markedly higher in the G+/LVH+subjects than the other groups(9.1±3.4P<.0001). There was no difference between G+/LVH-subjects and controls.Conclusions: MyBPC3genes is predominant causing mutations for HCM and account for15%of the genotyped patients in China. Severe hypertrophy and diastolic dysfunction of the disease are compatible with the presence of mutations in MyBPC3. Signs of regional diastolic abnormalities and LV remodelling are suggested to be a primary response to the mutations of MyBPC3expression.