Fibrinogen function is impaired in whole blood from patients with cyanotic congenital heart disease

Background

Patients with cyanotic congenital heart disease (CCHD) have haemostatic abnormities associated with bleeding and thrombo-embolic events. The haemostatic abnormalities are not fully understood, but recent studies indicate that elevated haematocrit and fibrinogen function may be of importance.The aim of this study was to characterise the haemostatic profile and examine the potential role of haematocrit on clot formation and strength in CCHD patients. Furthermore to examine whether CCHD patients with history of haemoptysis have diminished fibrinogen function compared to those without haemoptysis.

Methods

In a prospective study 75 adult CCHD patients had haematocrit, platelet count, and plasma fibrinogen concentration examined. Furthermore thrombelastography(TEG) as well as TEG Functional Fibrinogen(TEG FF) assay evaluating fibrinogen function(FLEV) was performed. Data were compared with historical data regarding previous haemoptysis in CCHD patients.

Results

Haematocrit was 57 ± 8% and platelet counts in the lower normal range. TEG revealed a hypocoagulable condition with impaired clot formation. TEG values were correlated to haematocrit, indicating that elevated haematocrit causes impaired clot formation and strength. Despite high levels of plasma fibrinogen, TEG FF demonstrated that FLEV was diminished and negatively correlated to haematocrit. Furthermore CCHD patients with previous history of haemoptysis had significantly lower FLEV compared to CCHD patients without haemoptysis.

Conclusion

Patients with CCHD are hypocoagulable mainly due to impaired fibrinogen function. Despite a low platelet count, platelet function does not seem to be severely affected in CCHD patients. Haemostasis, and especially fibrinogen function, is negatively affected by elevated haematocrit, and fibrinogen function is diminished in CCHD patients with haemoptysis.     

The pathogenesis of heart failure in infants with congenital heart disease.

BACKGROUND: The clinical symptoms of heart failure in infants with left-to-right shunts are thought to be explained by well-known hemodynamic disturbances such as pulmonary hypertension and overcirculation, but previous studies have not, thus far, found the expected correlations with hemodynamic and clinical parameters. Based on the neurohormonal model of heart failure, we hypothesised that the clinical symptoms of infants with left-to-right shunts are also related to neurohormonal disorders. METHODS: We compared various neurohormonal and hemodynamic parameters measured invasively in 70 infants with left-to-right shunts to the respiratory rate and gain in weight over a corresponding period of time. Heart rate correlated significantly with respiratory rate (r = 0.62***, p < 0.001) and gain in weight (r = -0.31*, p = 0.015), but more conventional measures of severity, such as the ratio of pulmonary to systemic flows, failed to show comparable correlations with clinical symptoms. Respiratory rate was related to levels of norepinephrine (r = 0.47***, p < 0.001) and plasma renin activity (r = 0.65***, p < 0.001). The important impact of autonomic imbalance on respiratory rate was underlined by an analysis of variability of heart rate in 26 infants that showed significantly reduced values for the domains of time and frequency. We were not able to find a conclusive multiple regression model with which to explain the symptom "failure to thrive". CONCLUSIONS: A increased heart rate, reduced variability in heart rate, and elevated levels of norepinephrine and renin are significant predictors of clinical symptoms such as tachypnea in infants with congenital cardiac malformations. The neurohormonal hypothesis, in which heart failure is interpreted not only as a hemodynamic derangement but also as a neurohormonal disorder, may be valid for infants with congenital cardiac malformations.     

Ambulatory heart rate is underestimated when measured by an ambulatory blood pressure device.

OBJECTIVE: To test the validity of ambulatory heart rate (HR) assessment with a cuff ambulatory blood pressure (ABP) monitor. DESIGN: Cross-instrument comparison of HR measured intermittently by a cuff ABP monitor (SpaceLabs, Redmond, Washington, USA), with HR derived from continuous electrocardiogram (ECG) recordings (1) in a controlled laboratory experiment and (2) during long-term recording in a true naturalistic setting. PARTICIPANTS: Six normotensive subjects participated in the laboratory study. A total of 109 male white-collar workers underwent ambulatory monitoring, of which 30 were mildly hypertensive. METHODS: Four different laboratory conditions (postures: lying, sitting, standing, walking), repeated twice, were used to assess the short-term effects of cuff inflation on the HR. To test the actual ambulatory validity, participants simultaneously wore a continuous HR recorder and the ABP monitor from early morning to late evening on 2 workdays and one non-workday. Diary and vertical accelerometery information was used to obtain periods of fixed posture and (physical) activity across which HR from both devices was compared. RESULTS: Laboratory results showed that the ABP device reliably detected HR during blood pressure measurement, but that this HR was systematically lower than the HR directly before and after the blood pressure measurement. The ambulatory study confirmed this systematic underestimation of the ongoing HR, but additionally showed that its amount increased when subjects went from sitting to standing to light physical activity (2.9; 4.3 and 9.1 bpm (beats/min), respectively). In spite of this activity-dependent underestimation of HR, the correlation of continuous ECG and intermittent ABP-derived HR was high (median r= 0.81). Also, underestimation was not different for normotensives and mild hypertensives. CONCLUSIONS: A direct effect of cuff inflation leads to the underestimation of ongoing HR during cuff-based ABP measurement. Additional underestimation of HR occurs during periods with physical activity, probably due to behavioural freezing during blood pressure measurements. HR underestimation was not affected by hypertensive state. When its limitations are taken into account, ABP-derived ambulatory HR can be considered a reliable and valid measure.     

Tei指数及脑钠肽评估先天性心脏病婴儿术前左心功能的研究

目的探讨检测血清脑钠肽浓度结合左心室Tei指数评估先天性心脏病婴儿术前左心功能的临床应用价值。方法选择先天性心脏病患儿60例为试验组,同期小儿外科住院患儿20例为对照组,将心功能分为四级,用多普勒超声心动图测量左心室Tei指数及左心室射血分数,采用酶联免疫吸附法(ELISA)检测血清BNP浓度。结果患儿血清BNP浓度、左心室Tei指数在心功能0级、Ⅰ级、Ⅱ级、Ⅲ级组呈逐渐增高趋势,左心室射血分数呈逐渐减低趋势,且方差分析显示各组间均数比较,差异有统计学意义(P0.01)。直线相关分析显示,血清BNP浓度与左心室Tei指数、心功能分级具有良好的正相关关系(r1=0.73,P0.01;r2=0.62,P0.01),与左心室射血分数具有负相关关系(r3=-0.48,P0.01);左心室Tei指数与心功能分级呈正相关关系(r4=0.57,P0.01),与左心室射血分数呈负相关关系(r5=-0.52,P0.01);左心室射血分数与心功能分级呈负相关关系(r=-0.56,P0.01)。结论 Tei指数及血清BNP浓度能够迅速、准确评估术前先天性心脏病婴儿心功能,具有临床推广应用价值。     

Transesophageal echocardiography in infants and children with congenital heart disease.

TEE applications for children and infants with congenital heart disease are now clinically established and TEE is being used in most major pediatric cardiovascular centers. This technology has evolved to the point that it is capable of providing diagnostic quality imaging, even for small infants. With expanding technology and increasing experience, new and more sophisticated applications will be found for pediatric TEE.     

Catecholamine stimulation is associated with impaired myocardial O(2) utilization in heart failure

OBJECTIVES: To investigate the effect of alpha,beta(1) and beta(2) adrenergic receptor (AR) stimulation on coronary hemodynamics, myocardial oxygen consumption (M(v)O(2)) and metabolic substrate preference in advanced dilated cardiomyopathy (DCM). METHODS: We studied 19 conscious, instrumented dogs with pacing-induced DCM. We evaluated systemic, coronary hemodynamics and M(v)O(2) in response to norepinephrine (NOR, 0.05-0.4 microg/kg per min), dobutamine (DOB, 1-10 microg/kg per min), phenylephrine (PHE, 1-5 microg/kg per min) and isoproterenol (ISO, 0.05-0.4 microg/kg per min) alone or in the presence of metoprolol (ISO+MET). Experiments were conducted in control state and in advanced DCM, 4-5 weeks after the initiation of pacing. RESULTS: Contractile responses (LV dP/dt) to catecholamines were desensitized and accompanied by a parallel decrease in heart rate-adjusted myocardial O(2) consumption (M(v)O(2/beat)), when alpha(PHE) or beta(1) (DOB) or both alpha/beta(1) (NOR) AR were stimulated in DCM. This was due to impaired transmyocardial (Ao-Cs) O(2) extraction rather than limitations in CBF responses. There was an associated shift in myocardial metabolism, evidenced by an increased preference for glycolytic substrates (Respiratory Quotient) following administration of any of these three adrenergic agonists in DCM. Combined beta(1)/beta(2) stimulation with ISO or beta(2)-AR stimulation (ISO+MET) in DCM resulted in greater M(v)O(2/beat), [(Ao-Cs) O(2)] extraction, and decreases in myocardial RQ consistent with a shift toward oxidation of FFA. CONCLUSIONS: The impairment in contractile responses to dobutamine and norepinephrine in DCM is associated with impaired myocardial O(2) extraction, and a shift toward a preference for glycolysis. A different myocardial metabolic pattern suggestive of increased oxidation of FFA with increased myocardial O(2) extraction was observed in the presence of combined beta(1)/beta(2) stimulation with isoproterenol or beta(2) stimulation (ISO+MET). These data suggest that beta(2)-AR stimulation in DCM shifts substrate preference toward FFA oxidation associated with greater M(v)O(2) requirements. These findings identify a putative metabolic effect of beta(2) -AR in DCM that may be deleterious.     

Thrombo-hemorrhagic liability in children with congenital heart diseases

Background

The precise mechanisms of the increased incidence of hemostatic abnormalities in congenital heart disease (CHD) have not been determined. The aim of the study was to evaluate some indicators of activation of platelets and vascular endothelial cells in patients with CHD, evaluation of bleeding liability of these patients, and correlation with the clinical presentation of these patients.

Sternal wound and mediastinal infections in infants with congenital heart disease.

The objective was to describe the epidemiologic, clinical, bacteriologic and therapeutic features of seven infants who developed sternal wound and mediastinal infections following palliation and/or repair procedures for congenital heart disease. A retrospective chart review was used. All infants with sternal wound and mediastinal infections were < 30 days of age at the initial operative procedure. Six of the infants had hypoplastic left heart syndrome, and one had complete transposition. Two infants required delayed closure of their chest wound. Three infants had superficial sternal infections and presented at a mean of 12 days postoperatively. Four infants had infection of the deep mediastinal structures: they were all asymptomatic and had purulent collections in their mediastinum at their second palliative operation, which was performed at a mean of 120 days after the initial surgery. Staphylococcus aureus, or coagulase-negative Staphylococcus, was isolated from the wound and/or blood of six infants. All infants with mediastinal infections were managed with operative debridement. Infants with superficial infections underwent local debridement. All infants received long-term intravenous antibiotics. Mediastinal infections in infants undergoing palliative staged procedures for congenital heart lesions may be chronic and indolent, resulting in delayed repair of congenital heart lesions.     

Transesophageal real-time echocardiography in infants and children with congenital heart disease.

Transesophageal echocardiography using Doppler color flow mapping with both single plane transverse and longitudinal pediatric probes was performed in 127 infants and children both intraoperatively and postoperatively. The 127 patients ranged in age from 1 day to 18 years (mean 37 months) and in weight from 2.4 to 45 kg (mean 13.2); 157 studies were successfully performed (100% of attempted) with no complications. Transesophageal two-dimensional echocardiography combined with pulsed wave Doppler ultrasound and color flow mapping provided detailed morphologic as well as physiologic information, with additional information provided overall in 56% of the cases. Typical limitations of single-plane transverse imaging were overcome using a prototype longitudinal-axis pediatric probe. Both left and right ventricular outflow tracts, distal pulmonary arteries and all of the interventricular and atrial septa were visualized. Assessment of surgical repair intraoperatively as well as assessment postoperatively for cardiac function, residual intracardiac shunts, residual valvular sequelae and other hemodynamic events was important and easily performed in an otherwise inaccessible patient. Transesophageal echocardiography in infants and in small children is a valuable "noninvasive" imaging technique that offers important additional and complementary information.     

1O公斤以内婴幼儿复杂先天性心脏病的体外循环管理

目的总结106例10kg以内婴幼儿复杂先天性心脏病的体外循环（extracorporeal circulation,ECC）管理体会。方法回顾性分析2009年1月至2010年12月在广州军区医院住院的106例10kg以内婴幼儿复杂先天性心脏病的临床资料和ECC资料。分析全组患儿ECC预充液的组成,不同温度时对灌注流量的要求;重视血液和各脏器的保护,行常规超滤和改良超滤以维持液体出入量的平衡。结果体外循环时间45～354min,主动脉阻断时间18～228min,转流中尿量10～300mL。术后死亡4例,与ECC无直接关系。结论合理的预充,充分的引流与有效的灌注流量,联合应用常规超滤、平衡超滤和改良超滤,重视血液和各脏器的保护是管理低体质量婴幼儿复杂先天性心脏病ECC的有效方法。     

Digital subtraction angiography in infants and children with congenital heart disease.

Digital subtraction angiography was used as the sole imaging technique in 95 infants and children aged 13 hours to 16 years undergoing cardiac catheterisation for the investigation of congenital heart disease. Injections of diluted contrast medium were made selectively at central sites, and the images were obtained using continuous image intensification fluoroscopy at either 32.25 nC/kg/s (125 microR /s) or 129 nC/kg/s (500 microR /s). In all cases images adequate for diagnosis and management were obtained with appreciably less contrast medium and a lower radiation dose than in a comparable group of patients using conventional biplane cineangiography. Thus digital subtraction angiography is a viable alternative to biplane cineangiography for children with congenital heart disease.     

Unusual stents in infants with severe congenital heart disease

Two infants with severe congenital heart disease requiring intervention are described. Although both required conventional surgical therapy, mitigating circumstances led to catheter intervention for short-term palliation. The feasibility and advisability of such procedures is discussed.     

Alfentanil in infants and children with congenital heart defects

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 tag/kg, alfentanil, 20 μg/kg, was given, followed by a continuous infusion of 1 μgkg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 μ/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartments moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 ± 2. mL/kg/min and 6.3 ± 0.8 mL/kg/min, respectively. Distribution volume was 0.48 ± 0.12 L/kg and 0.31 ± 0.08 L/kg, and elimination half-life was 69 ± 25 min and 62 ± 9 min, respectively. It is concluded that a continuous infusion of alfentanil as a supplement to nitrous oxide-halothane anesthetic is a feasibly method of anesthesia in infants and children undergoing surgery for correction of congenital heart defects.