Real-Time Three-Dimensional Echocardiographic Study Of Cardiac Function And Survival On Single Ventricle Anatomy

BACKGROUND AND PURPOSE Functionalsingle ventricle anatomy is the rare complicated congenital heart disease.The incidence is about 1/6500 new live birth.The term is used to describe a functional single ventricle regardless of anatomic subtype.The functional ventricle provides a common mixing chamber and pumps both the pulmonary and systemic circulations.Because Pulmonary and systemic circulations are parallel connection,neonates with single ventricle will develop decreased ventricular function and have a very high morbidity and mortality without palliative medical and surgical intervention.Conventional echocardiographic assessment of single ventricle anatomy is largely qualitative.Qualitative two dimensional echocardiography is the most widely used clinical assessment for single ventricle patients. But Assessment of ventricular function in patients with single ventricle anatomy is a challenging task for conventional two dimensional and Doppler echocardiography.Three dimensional echocardiography allows for the same ease and portability of two dimensional echocardiography, and published data demonstrates that two dimensional echocardiography compares well with cardiac magnetic resonance imaging in evaluation of single ventricular function.There is nice feasibility and reliability of real time matrix- array 3- dimensioanl echocardiography measurements of single-ventricle volumes and ejection fraction in young patients.Exploring the function of the heart is helpful to reveal the pump work of the cardio, but also a key for understanding the hemodynamics and pathology of the cardiovascular system of single ventricle in different stage operation.There are specific characteristics on clinical hemodynamic feature among surgery stages.The changes associated with surgery are necessary to be monitored.What is more is that they could give clue about the situation of the diagnosis Quantitative evaluation of the systemic ventricular performance by real-time three dimensional echocardiography might provide insight into the pathophysiology of this disease and can potentially aid and assess therapeutic interventions.Patients with single ventricle have to experience diverse palliative procedures leading to the Fontan operation.Staged palliation of single ventricle is associated with significant hemodynamic derangement,morbidity and mortality.The goal of surgical intervention is to improve hemodynamics and thereby relieving cyanosis and volume overload.Although significant advances have been made in medical and surgical management strategies for children with single ventricle.However,the long-term mortality of patients with single ventricle still remained low level.In order to improve survivals,most published studies tried to explore and identify a series of risk factors,which were likely to having association with specific anatomic abnormality,surgery operation,age and other clinical factors. However,the results were inconsistent and not quantitative.Little data existed in the risk factors that reliably predicted adverse clinical outcomes.This study included three parts as follow:Part 1 Utility of real time three-dimensional echocardiography in evaluation of cardiac function in children with single ventricle anatomyThe purpose of this part to evaluated systolic ventricular function by both 2-dimensioanl echocardiography and 3-dimensioanl echocardiography in 63 children with a functional single ventricle.To study the feasibility and reliability of real time matrix-array 3-dimensioanl echocardiography measurements of single-ventricle volumes and ejection fraction in young patients.The 2-dimensioanl echocardiography qualitative assessment of function by two independent experienced observers was compared with the 3-dimensioanl echocardiography derived ejection fraction(EF).2-dimensioanl echocardiography qualitative function was scored as 4(normal),3(mildly depressed),2(moderately depressed),or 1(severely depressed).Real-time 3DE was performed using a Philips IE33 system with an X7-2 pediatric transducer and full volume acquisition.Data were analyzed off line.The endocardial borders were traced manually during peak systole and end diastole using 8 long axis images by rotating around the center of the single ventricle.Results showed that①As a group,mean function by 3-dimensioanl echocardiography EF was 47.9%±11.31%.②2-dimensioanl echocardiography assessment of function by both observers individually had only moderate correlation with 3-dimensioanl echocardiography ejection fraction(Spearman's r = 0.50,0.65 respectively ).③When 3-dimensioanl echocardiography EF were defined:＞55%normal(4) and＜55%,＜45%,＜30%were used as mild(3),moderate(2) and serely depressed(1) function,linear regression analysis of 2-dimensioanl echocardiography versus EF revealed an r value of 0.66,with y = 0.6058 x + 1.79.④The 2-dimensioanl echocardiography interobserver agreement of ventricular function was moderate(kappa =0.5).⑤21 cases of 63 had complete cardiac catheterization examination.There was an excellent significance between EDV,ESV,EF derived from RT3DE and cardiac catheterization(r=0.743,r~2=0.5519,P＜0.01).⑥There are superior reproducibility between Intra-inter observers on all estimations(ICC＞0.95,P＜0.01 respectively). Part 2 Assessment of Staged Palliation of Hypoplastic Left Heart Syndrome by Real- time Three Dimensional EchocardiographyThe purpose of this part to estimate the cardiac function among different stages of surgery on functional single ventricle.A feasibility study was performed by prospectively enrolling patients with HLHS,pre- and post-Norwood,post-bidirectional cavopulmonary connection(BCPC).Transthoracic real time 3-dimensional echocardiography was performed using a X7-2 matrix array transducer and an IE33 ultrasound system(Philips Medical Systems).Volumetric data were analyzed offline using 4D Cardio-View (TomTec Imaging Systems) to determine end-diastolic and end-systolic volumes,and ventricular mass,and to derive ejection fraction(EF),stroke volume,cardiac index(CI), and mass/volume ratio of the systemic ventricle.For patients who received surgical palliation,the study was performed after the patient no longer required care in the intensive care unit.Results were compared using unpaired,two-tailed Student t-test.①There were a trend of increased EDV,EDVI,ESV,SV,MASS,and MPI were with the stages of operation. Compared with pre-Norwood state,both post-Norwood stageⅠpalliation and post stageⅡare associated with a trend of increased EDV,ESV,SV respectively.②Compared with pre-Norwood state,post-Norwood stageⅠpalliation was associated with a trend of decreased MASSI,MASS/Vol respectively.On the contrary,post-Norwood stageⅡpalliation was associated with a trend of increased MASSI,MASS/Vol respectively. But there was no statistically significant on these data from patients difference among 3 stages.③There was no statistically significant on EF from patients difference among 3 stages.EF had improved performance(EF of 40 to 43%),reflecting the un-loading of the systemic ventricle.④When comparing the no surgery patients,there appears to be a continuing trend on decreasing CO.But,CO had statistically significant elevation in patients with post stageⅡoperation.⑤When comparing the BCPC with presurgical patients,there appears to be a continuing trend on decreasing CI.⑥Myocardial performance index had weak correlation with ejection fraction from 3- dimensional echocardiography.The correlative coefficient was -0.330,p =0.043＜0.05.Part 3 Ejection Fraction by Real-time 3D Echocardiography Predicts Adverse Outcomes in Functional Single Ventricle PatientsThe purpose of this part to analyze the risk factor of functional single ventricle survival.From August,2006 to May,2009,a total of 95 patients with single ventricle(age 3.3±4.0 years,M/F 58/37) were prospectively enrolled in this study.Demographic variables and quantitative real-time 3D echocardiographic(QRT3DE) variables(ventricular volumes(EDV and ESV),stroke volumes(SV),ejection fraction(EF) were obtained. Real-time 3D echocardiography was performed using a Philips IE33 system with an X7-2 matrix array transducer.Off line analysis was made using a TomTec workstation and a rotational 8-plane Simpson method for EDV,ESV,SV and EF.Adverse outcomes were defined as death,and listing for/receiving heart transplantation.Results showed overall adverse outcomes occurred in 20%of patients(n=95) during follow-up(3.1±4.0 years). Between the 2 groups with(Group 1,n=19) or without(Group 2,n=76) adverse outcomes, there were significant differences in weight,height,BSA,HLHS for the clinical variables, as well as in EF,SV for QRT3DE variables.Uni-variant analysis demonstrated that BSA, weight,height,HLHS,and as well as EDV,SV,and EF were risk factors for adverse outcomes(p＜0.05).Overall survival after birth was 74.8±5.6%at 10 years.By Cox regression model analysis,EF and BSA were demonstrated as favorable prognostic factors. Using cut-offs of global single ventricular systolic function(EF)＞50%(normal),40～50% (mildly diminished),30～40%(moderately diminished) and＜30%(severely diminished), the subgroup with EF(30～40%) was associated with significantly increased adverse outcomes;and the subgroup with EF＜30%with a precipitous deterioration in outcome.In this group,2 of all 5 patients experienced adverse outcome during follow up. CONCLUSIONS①In patients with functional single ventricles,qualitative 2DE assessment of ventricular function has only moderate correlation with 3DE derived EF,with 2DE generally estimating function greater than 3DE.The reproducibility for 2DE qualitative assessment was only modest.In patients with single ventricle physiology, 3DE may provide a more reliable option for clinical decision making than 2DE. Further study is warranted to investigate the prognostic value of these methodologies.②In young pediatric patients with a functional single ventricle,real time 3DE measurement of volume and ejection fraction compare well with those obtained by cardiac catheterization.3DE will provide an important modality for the serial analysis of ventricular size and performance in young patients with functional single ventricles.③This small cohort suggests that RT3DE offers an opportunity to study staged palliation of HLHS.This methodology may be particularly useful in longitudinal follow-up in patients with staged palliation of HLHS and to guide therapy and assess the efficacy of therapeutic intervention.④Our study suggests that in addition to the known clinical variables(age,weight, height and BSA),QRT3DE derived functional measures are risk factors for adverse outcomes in patients with FSV.Furthermore,EF＜40%is associated with significant adverse outcomes,and EF＜30%rapid deterioration.Longitudinal follow-up of EF and timely intervention are warranted in these subgroups of FSV.