Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Ventricular synchronicity: observations comparing pulse flow and tissue Doppler assessment in a Chinese healthy adult cohort.

BACKGROUND: Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge about cardiac timing in healthy persons is scarce. Therefore, in the current study, we sought to investigate the physiological status of interventricular synchronicity using pulse wave flow and tissue Doppler imaging in a healthy Chinese population. METHODS: Eighty-eight healthy volunteers underwent standard flow and tissue Doppler echocardiographic examinations. Ventricular inflow and outflow pulse wave flow Doppler patterns were recorded together with annulus pulse tissue Doppler imaging. Time intervals from the beginning of the QRS complex to the onset, peak and end of each wave were measured. RESULTS: The onsets of systole between left and right ventricles were highly synchronized by both imaging modalities. However, the left ventricle reached the peak flow ejection and peak mechanical contraction earlier than the right ventricle, (165.61 ± 26.23) ms vs. (204.3 ± 34.55) ms (P < 0.01) and (133.62 ± 26.19) ms vs. (191.25 ± 38.47) ms (P < 0.01). Time to peak early diastolic relaxation was earlier in the left ventricle than in the right heart, (500.23 ± 56.52) ms vs. (524.94 ± 47.42) ms (P < 0.01). CONCLUSIONS: Left and right ventricles were well synchronized at the onsets of systole and diastole even though interventricular peak systolic and peak early diastolic dyssynchrony was observed in healthy people by pulse wave Doppler imaging. In addition, diastolic timing events were slightly affected by age and gender.

[Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy].

OBJECTIVE: To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype. METHODS: Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms. RESULTS: Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype. CONCLUSIONS: Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.

Importance of dynamic dyssynchrony in the occurrence of hypertensive heart failure with normal ejection fraction.

AIMS: The impact of haemodynamic stress on left ventricular (LV) dyssynchrony in heart failure with normal ejection fraction (HFNEF) remains unknown. We sought to evaluate the relationship and predictive value of dynamic changes of LV dyssynchrony on hypertensive HFNEF. METHODS AND RESULTS: A total of 131 subjects including 47 hypertensive HFNEF patients, 34 hypertensive patients with left ventricular hypertrophy (LVH) without HFNEF, and 50 normal controls were studied by dobutamine stress echocardiography with tissue Doppler imaging. Systolic and diastolic dyssynchrony were assessed using the LV six-basal-six-mid-segment model and cut-off values were derived from normal controls. The mean basal segments longitudinal systolic (mean Sm) and early diastolic (mean Em) velocities were measured. In normal controls, systolic and diastolic dyssynchrony did not develop during stress. The prevalence of resting systolic (36.2% vs. 38.2%, P = 0.85) and diastolic (34.0% vs. 29.4%, P = 0.66) dyssynchrony was similar in HFNEF and LVH groups. During stress, the prevalence of systolic and diastolic dyssynchrony increased dramatically to 85.1% and 87.2%, respectively, in HFNEF group, but only 52.9% and 58.8% in LVH group (P < 0.005). In HFNEF group, stress-induced increase in mean Sm was significantly blunted (2.8 ± 2.0 vs. 4.2 ± 2.4 cm/s, P = 0.004), and the increase was abolished for mean Em (-0.3 ± 2.5 vs. 2.4 ± 3.4 cm/s, P < 0.001). On multivariate analysis, stress-induced changes in mean Em (OR = 0.69, P = 0.004) and mean Sm (OR = 0.56, P = 0.004), and diastolic (OR = 4.6, P = 0.005) and systolic dyssynchrony during stress (OR = 4.3, P = 0.038) were independent determinants for occurrence of HFNEF. CONCLUSION: Dynamic dyssynchrony during stress and impaired myocardial longitudinal function reserve are characteristics of HFNEF.

[Novel MYBPC3 mutations in Chinese patients with hypertrophic cardiomyopathy].

OBJECTIVE: To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced. RESULTS: Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients. CONCLUSION: MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.

[Therapy for replenishing qi, nourishing yin and promoting blood circulation in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a randomized controlled trial].

BACKGROUND: No-reflow phenomenon after reperfusion treatment of acute myocardial infarction (AMI) is becoming more recognized today. The effective treatment for no-reflow has not been reported. OBJECTIVE: To observe the effects of traditional Chinese medicine (TCM) therapy for replenishing qi, nourishing yin, and promoting blood circulation on AMI patients undergoing percutaneous coronary intervention (PCI). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted from January 2005 to March 2006 using a double-blinded, randomized method. Thirty-five AMI patients (Killip I-II) were first diagnosed as ST segment elevation AMI and obtained primary PCI. They were recruited from People's Hospital, Peking University. All patients' symptoms accorded with qi-yin deficiency syndrome and blood stasis syndrome. They were randomly and double blindly divided into control group (18 cases) and treatment group (17 cases). The patients in the control group received Western medicine treatment, and the patients in the treatment group were treated with Western medicine plus American ginseng and Salviae miltiorrhizae preparations. They were all treated for 3 months. MAIN OUTCOME MEASURES: Before and after 3-month treatment, the TCM symptoms were observed and scored. At the state of baseline and dobutamine stress, left ventricular ejection fraction (LVEF), wall motion score (WMS), WMS index and normal cardiac muscle percentage (NCMP), and the myocardial contrast echocardiography index k, which reflects myocardium microcirculation perfusion, were detected. RESULTS: After 3-month treatment, the TCM symptoms in the treatment group were improved as compared with the control group (X(2)=4.118, P=0.042). At the state of dobutamine stress, LVEF in the treatment group after treatment was higher than those in the control group (t=2.130, P=0.041) and before treatment (t=2.345, P=0.032). Although the number of the segments with increased k value was more than that in the control group, there was no significant difference. CONCLUSION: TCM therapy for replenishing qi, nourishing yin and promoting blood circulation can improve the clinical symptoms and quality of life of the AMI patients undergoing PCI, and is beneficial to myocardium microcirculation. Thus, it may be an alternative cardioprotective treatment strategy for successful myocardial microcirculation in AMI patients after reperfusion.

Effect of Chinese drugs for supplementing Qi, nourishing Yin and activating blood circulation on myocardial perfusion in patients with acute myocardial infarction after revascularization.

OBJECTIVE: To observe the effects of Chinese drugs for supplementing qi, nourishing yin and activating blood circulation on the myocardial perfusion in acute myocardial infarction (AMI) patients after revascularization. METHODS: Eighty patients with anterior or inferior ventricular wall AMI, who had received revascularization by intravenous thrombolysis or coronary bypass, were randomized into the treated group and the control group equally, both treated with conventional Western medical treatment, but combined, respectively, with Xinyue Capsule (, XYC) plus Composite Salvia Tablet (CST) and placebo for 3 months. Dobutamine stress echocardiography (DSE) was performed 14 days and 3 months after revascularization, respectively on every patient to observe blood perfusion extent (b value), myocardial perfusion velocity (k value) and local blood fl ow volume (k x b) in left ventricular infarction-related vascular segments under stressed state. RESULTS: With 5 cases dropping out in the observation period (3 in the treated group and 2 in the control group), the trial was completed in 75 patients in total. The 14-day DSE shows that the b value and k x b value of left anterior ventricular wall mid segment and apex segment, and the k value of apex segment in patients with anterior wall AMI, as well as the b value and k x b of basal segment in patients with inferior wall AMI in the treated group were significantly higher than those in the control group (P<0.05 or P<0.01). The 3-month DSE shows that the b value of apex segment, k x b value of basal segment, mid segment and apex segment of left anterior ventricular wall in patients with anterior wall AMI as well as the b value and k x b value of basal segment of left inferior ventricular wall in patients with inferior wall AMI were all higher in the treated group than those in the control group, respectively (P<0.05). The comparison between 14-day DSE and 3-month DSE in the treated group showed that the b value of apex segment of left anterior ventricular wall in patients with anterior wall AMI and the k x b value of apex segment and mid segment of left inferior ventricular wall in patients with inferior wall AMI significantly increased along with the on-going treatment (P<0.05). CONCLUSION: Therapy with Chinese drugs for supplementing qi, nourishing yin and activating blood circulation in combination with conventional Western medical treatment could obviously improve the blood perfusion at the myocardial tissue level in infarction-related vascular segments.

Ventricular transmural repolarization sequence: its relationship with ventricular relaxation and role in ventricular diastolic function.

AIMS: We investigated the role of ventricular repolarization sequence in ventricular diastolic function. METHODS AND RESULTS: Arterially perfused canine left ventricular wedge preparation with simultaneous recording of action potentials and isometric contractile force was used to establish the relationship between ventricular repolarization and relaxation sequences. An isolated rabbit working heart model was used to investigate role of ventricular repolarization sequence in ventricular diastolic function. Under controlled conditions, similar to transmural dispersion of repolarization (TDR), there existed a time difference between initiation of epicardial and endocardial relaxation (TR(Epi-Endo), 47.4 +/- 13.9 ms) with epicardium relaxing earlier. There was a strong correlation between TDR and TR(Epi-Endo) (r(2) = 0.99, n = 5) and the interventions that changed transmural repolarization sequence led to parallel changes in transmural relaxation sequence. In isolated rabbit working hearts, reversal of the transmural repolarization sequence that manifested as negative T wave was associated with a significant increase in isovolumic relaxation time (from 49.2 +/- 19.1 to 76.4 +/- 12.1 ms, n = 5, P = 0.001). CONCLUSION: There is a strong correlation between transmural repolarization and relaxation sequences. A positive T wave that denotes transmural repolarization sequence from epicardium to endocardium is essential for normal diastolic function of ventricle and the reversal of such sequence is associated with ventricular diastolic dysfunction.

[Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype].

OBJECTIVE: The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM). METHODS: There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype. RESULTS: Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2. CONCLUSIONS: Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.

[The relationship between TIMI (thrombolysis in myocardial infarction) risk score and efficacy of conservative or interventional strategy in patients with non-ST-segment elevation acute coronary syndromes].

OBJECTIVE: To investigate the relationship between thrombolysis in myocardial infarction (TIMI) risk score and efficacy of different treatment strategies in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: From Oct. 2001 to Oct. 2003, 545 consecutive patients with NSTE-ACS were randomly assigned to early conservative strategy (n = 284) or early invasive strategy group (n = 261). The combined cardiovascular events (a combination of cardiac death, nonfatal myocardial infarction, nonfatal heart failure and re-hospital admission due to recurrent ischemia angina) within 30 days and 6 months were analyzed and related to the TIMI risk score at admission. RESULTS: Rehospitalization due to recurrent ischemia angina of 30 days and the combined cardiovascular events of 30 days and 6 months were significantly lower in early invasive strategy group (3.5%, 10.0%, 21.1%) compared with early conservative strategy group (8.1%, 16.9%, 28.2%, all P < 0.05). Subgroup analysis indicated early invasive strategy could significantly decrease the 30 d incidence of the combined end point events in patients with high TIMI risk score and the 6 months incidence of the combined end point events in patients with moderate and high TIMI risk score (all P < 0.01), but the incidence was similar between the two different strategies in patients with low TIMI risk score. CONCLUSIONS: Early invasive strategy may significantly reduce combined cardiovascular events in NSTE-ACS patients with moderate and high TIMI risk score compared with early conservative strategy.

[Comparative study of gene mutation between Chinese patients with familial and sporadic hypertrophic cardiomyopathy].

OBJECTIVE: To compare the gene mutation between Chinese patients with familial and sporadic hypertrophic cardiomyopathy (HCM). METHODS: Peripheral blood samples were collected from 36 patients with familial HCM (FHCM) and 50 patients with sporadic HCM (SHCM), all un-related and from different provinces of China. PCR was used to amplify the 26 protein-coding axons of beta-myosin heavy chain (MYH7), 16 exons for cardiac troponin T (TNNT2), and 38 exons for cardiac myosin-binding protein C (MYBPC3). The amplified products were sequenced and compared with the standard sequence in the genBank so as to determine the potential mutation sites. RESULTS: (1) 13 of the 36 FHCM patients (36.1%) harbored 3 different mutations in MYH7 gene: Arg663His in exon18, Glu924Lys in exon 23, and Ile736Thr in exon 20. Of the 50 SHCM patients, only 1 (2%) harbored MYH7 gene missence mutation: Ile736Thr located in exon 20. (2) TNNT2 was not identified in all SHCM patients and FHCM patients. (3) MYBPC3 was not identified in all SHCM patients. Four FHCM patients harbored 2 different mutations: Arg502Trp in exon 18 and Arg346fs in exon 13 respectively. CONCLUSION: MYH7 and MYBPC3 may be the dominant disease-causing genes in Chinese familial HCM patients; however the mutation rate of MYH7 and MYBPC3 genes is significantly lower in the SHCM patients compared with the FHCM patients. TNNT2 seems not the predominant disease-causing gene in all Chinese patients with HCM.

[The effect of early invasive strategy on early and late outcomes in high-risk non-ST-segment elevation acute coronary syndromes].

OBJECTIVE: To investigate the effect of early invasive strategy on early and late outcomes in high-risk patients with non-ST-segment elevation acute coronary syndromes (ACS). METHODS: Five hundred and forty-five patients of ACS without ST-segment elevation were randomly assigned to an early conservative strategy (284 cases) or early invasive strategy group (261 cases), who were enrolled consecutively from Oct., 2001 to Oct., 2003. The combined cardiovascular events (a combination of cardiac death, nonfatal myocardial infarction, nonfatal heart failure and hospital readmission due to recurrent ischemic angina) within 30 days and 6 months were analyzed and the effects of early invasive strategy on early and late outcomes in high-risk patients with increased TnI or hs-CRP levels were evaluated. RESULTS: As compared with early conservative strategy, early invasive strategy lowered the rate of hospital readmission due to recurrent ischemic angina of 30 d and the combined cardiovascular events of 30 d and 6 months (all P < 0.05). Subgroup analysis indicated early invasive strategy could significantly decrease the incidences of the combined cardiovascular events of 30 d and 6 months and the hard end point events of 6 months in patients with increased TnI or hs-CRP levels (all P < 0.01), but no such changes could be seen in patients with normal TnI or hs-CRP levels, as compared with early conservative strategy. CONCLUSIONS: Early invasive strategy decreases significantly cardiovascular events and improves the early and late outcomes in high-risk patients with increased TnI or hs-CRP levels.

[A frame shift mutation, Arg346fs mutation, is identified in cardiac myosin-binding protein C gene in a Chinese family with hypertrophic cardiomyopathy].

OBJECTIVE: To explore the disease-causing gene mutation in Chinese with hypertrophic cardiomyopathy (HCM). METHODS: The peripheral venous blood samples were collected from 5 HCM families without consanguinity, including 5 probands, 2 males and 3 females, 28 sporadic HCM patients, 18 males and 10 females, and 80 healthy controls. The exons in the functional regions of cardiac myosin-binding protein C (MYBPC3) were amplified with PCR and the amplified products were sequenced. RESULTS: A frame shift mutation-Arg346fs mutation in exon 13, the first mutation identified in Chinese-was discovered in one family with HCM. However, the members of the same HCM family with the Arg346fs mutation showed differences in phenotype and prognosis. CONCLUSION: Cardiac myosin-binding protein C (MYBPC3) may be one of the main disease-causing genes. The heterogeneity of phenotype suggests that multiple factors may be involved in the pathogenesis.

[Mutations in beta myosin heavy chain gene: two mutations in Chinese with familial hypertrophic cardiomyopathy and the correlation between the genotype and phenotype].

OBJECTIVE: To study the disease-causing gene mutation in Chinese with hypertrophic cardiomyopathy (HCM), and to analyze the correlation between the genotype and phenotype. METHODS: Samples of peripheral blood were collected from five Chinese patients with HCM in whose families at least 2 HCM patients existed. The exon in the functional regions of the beta myosin heavy chain gene (beta-MHC) were amplified with PCR and the products were sequenced. The relation between the genotype and phenotype was analyzed. RESULTS: Two mutations were first identified. Eighty controls were normal in the genetic test. CONCLUSION: beta-MHC may be the main disease-causing gene. Two mutations have different phenotypes. In one family, the identical mutation has different phenotypes and prognoses. The heterogeneity of phenotype suggests that multiple factors be involved in the pathogenesis.