Postoperative Mortality And Respiratory Complications In Heterotaxy Patients With Congenital Heart Disease And Their Relationship With Ciliary Dysfunction

Congenital heart disease (CHD), one of the most common birth defects, affects approximately7.5%o-9%o of children and is the leading cause of death in infants younger than one year of age. The data from WHO shows that there are1.5million children born with CHD each year in the world, while in our country the data is150,000to200,000. Heterotaxy always combines with the most complicated CHD. CHD patients with heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. While this is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Recent studies have revealed an association among heterotaxy, congenital heart disease, and primary ciliary dyskinesia (PCD). Thus airway ciliary dysfunction (CD) similar to that of PCD may have relevance for increased respiratory complications in heterotaxy patients. We will compare mortality and respiratory complications in CHD patients heterotaxy with that in CHD patients without heterotaxy to explore the relation between heterotaxy and postsurgical mortality, as well as respiratory complications. We will recruit CHD patients with heterotaxy and also without heterotaxy as control to assess the incidence of CD by analysis of measurement of nasal NO and airway ciliary motion. Finally, we will recruit members from families with familial CHD to investigate the the role of Cilia in heart development. CHD These studies have the potential to transform patient care and provide the basis for future clinical trials to evaluate the efficacy of applying pre and postoperative pulmonary therapy to improve outcome for patients undergoing high-risk cardiac surgeries.PartⅠRetrospective study on postoperative mortality and respiratory complications in heterotaxy patients with congenital heart diseaseObjectiveExplore the mortality and respiratory complications in heterotaxy patients as compared to CHD patients without heterotaxy.Methods A retrospective review of patients undergoing cardiac surgery was undertaken at our hospiatl between Jan,1st,2000and Dec,31th,2011, which was performed on postsurgical outcomes of107patients with heterotaxy and congenital heart disease exhibiting the full spectrum of situs abnormalities associated with heterotaxy. As controls patients,867cardiac surgical patients with congenital heart disease, but without laterality defects, were selected, and surgical complexities were similar with a median Risk Adjustment in Congenital Heart Surgery-1score of3.0for both groups.ResultsWe found the postsurgical deaths (16.8%vs4.7%; OR,3.0), mean length of postoperative hospital stay (12.7vs9.1days) and mechanical ventilation(57vs42hours) were significantly increased in the heterotaxy patients. Also elevated were rates of prolonged ventilatory courses (6.5%vs2.1%; OR,3.1), critically ill notice (13.1%vs5.8%; OR,2.4), salvage (11.2%vs5.1%:OR,2.3), fever (66.4%vs34.9%; OR,3.7) and rales (30.0%vs18.9%:OR,1.8).ConclusionsOur findings show heterotaxy patients had more postsurgical events with increased postsurgical mortality and risk for respiratory complications as compared to control patients with similar Risk Adjustment in Congenital Heart Surgery-1surgical complexity scores. We speculate that increased mortaliy and respiratory complications maybe due to some respiratory defects in heterotaxy patients, such as ciliary dysfuntion.Part IIStudy on respiratory ciliary dysfunction in heterotaxy patients with congenital heart diseaseObjectiveExplore the effects of CD on increased respiratory complications in heterotaxy patients.Methods32CHD patients with heterotaxy were recruited, and51CHD patients without heterotaxy and100healthy persons were also recruited as controls.Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured by NO analyser; inter-observer and intra-observer agreements were determined for Ciliary motion assessment; suspectable nasal tissue was culture for discharging secondary CD.Results1. Thirteen patients(40.6%) exhibited CD characterized by abnormal ciliary motion among total32heterotaxy patients,8CD patients’ nNO levels appeared below or near the PCD cutoff values.2. Inter-observer and intra-observer agreements for ciliary motion assessment by videomicroscope were good.3.9nasal tissue samples with CD were cultured successfully, among which2samples were secondary CD.Conclusions1. Our studies show that CHD patients with heterotaxy have substantial risk for CD with low nNO.2. The method for ciliary motion assessment by videomicroscope is credible.3. Nasal tissue culture contributes to discharging secondary CD.Part ⅢStudy on respiratory ciliary dysfunction in members from families with familial CHD and members from heterotaxy nuclear familiesObjectiveExplore inheritance of Ciliary dysfunction.Methods:We assessed35members from5families with familial CHD for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; The number of Heterotaxy among33families with familial CHD was counted, and the number of families with familial CHD among53heterotaxy was also counted;We also assessed22heterotaxy nuclear families for airway CD and nNO.Results1.13patients (37.1%) exhibited CD characterized by abnormal ciliary motion and5(38.5%) patients with CD exhibited nNO levels below or near the PCD cutoff values.2. There were7heterotaxy patients among78CHD patients (9.0%) from33 families with familial CHD.3. There were7heterotaxy patients with with familial CHD among53heterotaxy patients (13.2%).4.49members were recruited from22heterotaxy nuclear families, among which9members (18.4%) from5individual nuclear families appeared CD.Conclusions1. Our studies showed that members from families with familial CHD have substantial risk for CD with low nNO.2. There was a high incidence of heterotaxy among patients with familial CHD, and there was a high incidence of patients with familial CHD among heterotaxy as well.3. Members from heterotaxy nuclear families have substantial risk for CD with low nNO, CD appeared apparente genetic predisposition.