Research Of Noninvasive Assessment Of Right Ventricular Function In Children With Tetralogy Of Fallot

Background:Previous studies have consistently revealed a central role for RV dysfunction in the prognosis and outcomes for a wide variety of acquired and congenital cardiac conditions. TOF is the most common cause of cyanotic congenital heart disease(CHD). Although TOF can be repaired surgically, the rate of progressive right ventricular(RV) dysfunction after operatidon reachs to 38.2%. The assessment of RV function is important in the management in TOF before operation and follow-up after operation. Yet, owing to its complex crescentic shape, the RV prove difficult to accurately and reproducibly assess. Reliable, noninvasive evaluation of right ventricular function, enable the identification of TOF with impaired cardiac function before they become clinically symptomatic is required. Tissue Doppler imaging(TDI),strain rate and strain analysis (a measure of deformation that can be derived from TDI data, may represent a new, powerful method for quantifying regional myocardial function and is less influenced by tethering effects than TDI) have the potential to assess ventricular function independent of the shape of the ventricle. It has been used widely in many acquired heart dieases, however, there is few report, especially preceding study about the technique used in CHD. Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and wall stress.It is well-recognized that BNP is raised in conditions with ventricular volume and pressure overload and has a diagnostic role in RV dysfunction. Up to now, It has few reported that TDI, strain rate and strain analysis derived from TDI have been used to assess the RV function in TOF patients before operation and early after repair of TOF, correlate with neurohormonal activation:N-terminal proBNP levels (NT-proBNP) and pathologic transform of the remodel of RV.Objectives:This study was designed to evaluate the indices obtained by TDI,strain rate and strain analysis and correlate these indices with neurohormonal activation:Plasma NT-proBNP levels, matrix metalloproteittases of plasma and cardiac muscle in TOF, The indices will be used as a non-invasive important indices of right ventricular dysfunction to diagnose, treatment and follow-up of RV function in patients with TOF.Methods:Thirty-seven children with TOF were included in the study as a TOF group, Thirty-two children of them who had been surgically repaired TOF served as a TOF6 group, Thirty-seven age-and body surface area (BSA)-matched healthy children served as a control group. Comprehensive echocardiographic examination were done to evaluate left and right ventricular function in the two groups. Peripheral venous blood samples were obtained from all participants.After a rest of 15 minutes, the blood samples were immediately placed on ice and subsequently centrifuged at 5,000 rpm for 10 minutes. Plasma were stored at 80℃until further analysis. Concentrations of plasma NT-proBNP was determined using an immunoassay. Six months to one year, echocardiographic examinationin and Plasma NT-proBNP survey were repeat in the surgically repaired TOF(TOF6 group). A subset of 20 patients had invasive measurement of pressure of every cavity and ejection fraction (EF) of LV and RV. Plasma mmp9 were measured by ELISA and IOD of mmp-9 and mmp-2 of myocardium obtained from patients of TOF were measured by immunohistochemistry.Result:1. The left and right ventricular function in TOF patients had not changed significantly showed in traditional echocardiographic parameters compared to control group; The results of TDI, strain rate and strain analysis derived from TDI showed that the systolic and diastolic function index of RV and LV were decreased before operation--- Systolic function index of RV and LV:peak systolic velocity (Sm), peak systolic strain rate (SRs), systolic strain (ε) and systolic excursion(D) by tissue tracking (TT) were reduced in the mid segments of free wall in patients with TOF compared to controls; Diastolic function index:early diastolic velocity (Em), Em/Am, peak early diastolic SR (Sre) were reduced, E/Em (the ratio of the peak transmitral flow velocity during early diastole (E) to the peak annular velocity during early diastole (Em) obtained by TDI) were increased in patients with TOF compared to the control group; The Time from onset of QRS to Sm (Q-Sm) and the ejection time of RV were reduced and myocardial relaxation time was longer. TDI showed that RV E/Em significantly correlated with RV end diastolic pressure (RVDP), however, the RV conventional echocardiographic parameters did not correlate with any invasive measure of RV function. Six months to one year after surgically repaired TOF, the index of systolic and diastolic function of LV were declined to normal, but the index of systolic and diastolic function of RV were not improved in the TOF6 group.2. There was no correlation of NT-proBNP to age and gender. Levels of NT-proBNP were elevated in the patients with TOF before and early after operation than control group. Howere, there was no significant difference between before and early after operation in TOF. Plasma NT-proBNP levels correlated significantly with LVAm obtained by TDI, SRs andεin the mid segments of free wall of RV obtained by strain rate and strain analysis and significantly correlated with central vena press(CVP) just after operation, but no correlated with the pressure of any cavity and EF of RV.3. IOD of mmp-2 of myocardium was significantly correlated IOD of mmp-9 of myocardium. IOD of mmp-9 or mmp-2 of myocardium was significantly negative correlated with Simpson's biplane RVEF and SRs in the mid segments of free wall of RV; postive correlated with the age of the patient and CVP just after operation. Level of plasma mmp9 was increased in TOF group than control group and significantly correlated with level of plasma NT-proBNP and LogNT-proBNP.Conclusion:Our group recently demonstrated that TDI variables, SR and Strain analysis derived from TDI data has the potential to assess RV function, appeared to be more sensitive indicators of RV myocardial dysfunction than conventional indices of RV function.RV dysfunction detected by TDI variables, SR and Strain analysis determination in asymptomatic or minimally symptomatic TOF patients correlated well with plasma NT-proBNP and IOD of mmp9. Thus, these simple non-invasive methods can be used additionally to help in assessing RV function in TOF with impaired cardiac function before they become clinically symptomatic. The increasing of MMPs expression in the plasma and myocardia have a relation to the structure and function of right ventricular remodeling in TOF.