Comparison of transpulmonary thermodilution and ultrasound dilution technique: novel insights into volumetric parameters from an animal model.

Especially in critically ill children with cardiac diseases, fluid management and monitoring of cardiovascular function are essential. Ultrasound dilution technique (UDT) was recently introduced to measure cardiac output (CO) and volumetric parameters, such as intrathoracic and end-diastolic blood volume. We compared UDT with the well-established transpulmonary thermodilution (TPTD) method (PiCCO) for determining CO measurements and derived volumes in a juvenile animal model. Experiments were performed in 18 ventilated, anesthetized piglets during normovolemia and after isovolemic hemodilution. At baseline and 20 min after each step of isovolemic hemodilution, 3 independent measurements of CO and volumetric parameters were conducted with TPTD and UDT, consecutively, under hemodynamically stable conditions. We observed comparable results for CO measurements with both methods (mean 1.98 l/min; range 1.12-2.87) with a percentage error of 17.3% (r = 0.92, mean bias = 0.28 l/min). Global end-diastolic volume (GEDV) and intrathoracic blood volume (ITBV) by TPTD were almost two times greater than analogous volumes [central blood volume (CBV); total end-diastolic volume (TEDV)] quantified by UDT (CBV = 0.58 × ITBV + 27.1 ml; TEDV = 0.48 × GEDV + 23.1 ml). CO measurements by UDT were found to be equivalent and hence interchangeable with TPTD. Discrepancies in volumetric parameters could either be due to the underlying algorithm or different types of indicators (diffusible vs. nondiffusible). Compared with the anatomically defined heart volume, TPTD seems to overestimate end-diastolic volumes. Future studies will be necessary to assign these results to critically ill children and to validate volumetric parameters with reference techniques.

Growth differentiation factor 15: an additional diagnostic tool for the risk stratification of developing heart failure in patients with operated congenital heart defects?

BACKGROUND: Many young adults who have congenital heart defects develop heart failure despite corrective surgeries. Growth differentiation factor 15 (GDF-15) has an established role as a marker for risk stratification and mortality both in patients after acute myocardial infarction and in patients with heart failure. Our aim was to establish a role for GDF-15 for monitoring heart failure in operated congenital heart defects (ACHD). This potential biomarker was validated through comparison with maximal oxygen uptake (VO(2max)) and to another biomarker, N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS: A total of 317 ACHD patients (129 females) with an average age of 26.5 ± 8.5 years (mean ± SD) enrolled in the study. We studied the relation between GDF-15 and NT-proBNP and VO(2max%) (percent predicted for age and gender). The cutoffs for the groups were as follows: NT-proBNP <100, 100 to 300, and >300 pg/mL; VO(2max%) <65%, 65% to 85%, and >85% of predicted normal. RESULTS: Significant differences in mean GDF-15 levels were found between the NT-proBNP <100 and NT-proBNP >300 groups, as well as between the 100 to 300 and the >300 groups. For VO(2max%), significant differences were found in GDF-15 levels between <65% and >85% and between <65% and 65% to 85%, respectively. The lowest mean GDF-15 was found in groups with NT-proBNP <100 pg/mL and VO(2max%) >85%. The highest mean GDF-15 was found in the groups with NT-proBNP >300 pg/mL and VO(2max%) <65%. A subgroup analysis, including 82 patients with operated tetralogy of Fallot, showed that patients in the New York Heart Association I class have significantly lower NT-proBNP and GDF-15 level and markedly higher VO(2max) compared with the patients in higher New York Heart Association class. CONCLUSION: Growth differentiation factor 15 might be used as a surrogate marker for latent heart failure and could help to identify patients with ACHD who are at risk for developing heart failure, even if they are clinically asymptomatic.

How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube.

The heart is the first organ to function in vertebrate embryos. The human heart, for example, starts beating around the 21st embryonic day. During the initial phase of its pumping action, the embryonic heart is seen as a pulsating blood vessel that is built up by (1) an inner endothelial tube lacking valves, (2) a middle layer of extracellular matrix, and (3) an outer myocardial tube. Despite the absence of valves, this tubular heart generates unidirectional blood flow. This fact poses the question how it works. Visual examination of the pulsating embryonic heart tube shows that its pumping action is characterized by traveling mechanical waves sweeping from its venous to its arterial end. These traveling waves were traditionally described as myocardial peristaltic waves. It has, therefore, been speculated that the tubular embryonic heart works as a technical peristaltic pump. Recent hemodynamic data from living embryos, however, have shown that the pumping function of the embryonic heart tube differs in several respects from that of a technical peristaltic pump. Some of these data suggest that embryonic heart tubes work as valveless "Liebau pumps." In the present study, a review is given on the evolution of the two above-mentioned theories of early cardiac pumping mechanics. We discuss pros and cons for both of these theories. We show that the tubular embryonic heart works neither as a technical peristaltic pump nor as a classic Liebau pump. The question regarding how the embryonic heart tube works still awaits an answer.

Intravenous luteinizing hormone-releasing hormone has no effect on serum N-terminal pro-brain natriuretic peptide in children and adolescents.

BACKGROUND: Little is known about the acute effects of i.v. luteinizing hormone-releasing hormone (LHRH) on the heart function, therefore the aim of the present study was to measure N-terminal pro-brain natriuretic peptide (N-BNP) in children, who underwent a diagnostic work up for short stature or delayed puberty. METHODS: N-BNP was measured in 52 children before and after administration of LHRH. Serum N-BNP obtained from 255 healthy children and adolescents (aged birth-18.3 years) served as a reference. RESULTS: There was no significant difference between baseline N-BNP of children who underwent the LHRH diagnostic test and their healthy peers. There was no significant serum N-BNP level change before or after administration of LHRH (59 +/- 36 pg/mL vs 58 +/- 34 pg/mL). N-BNP fell from 399 +/- 425 pg/mL in newborns and reached 44 +/- 36 pg/mL in children aged 12-18 years. CONCLUSION: Short stature or delayed puberty had no effect on heart function determined by serum N-BNP; i.v. LHRH does not acutely influence the level of serum N-BNP.

A new modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters.

This study describes a modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters: A device similar to that used in heart catherisation with a standard micro-introducer serving as sheath and an arterial catheter serving as inner dilator was pushed forward over a wire guide that had before been inserted via a peripheral venous catheter. With this method 2-and 3-French catheters could be safely inserted into peripheral veins of 14 paediatric patients. In conclusion successful insertion of a small peripheral venous catheter offers in most cases a possibility for the placement of a central venous line.

Chronotropic incompetence in adolescents and adults with congenital heart disease after cardiac surgery.

BACKGROUND: Chronotropic incompetence (CI) is one of the major problems in adults with congestive heart. Little is known about CI in adults with congenital heart disease (ACHD) after cardiac surgery. The purpose of our study was to investigate the presence and risk factors of CI in ACHD patients. METHODS AND RESULTS: Clinical and echocardiographic data, NT-pro brain natriuretic peptide (N-BNP), and peak oxygen uptake (VO2peak) during spiroergometry were obtained in 345 consecutive ACHD patients. CI was defined as the failure to achieve > or = 80% of the predicted maximal heart rate. A total of 117 (34%) of study patients fulfilled the CI criterion. These patients were in a higher New York Heart Association class (1.7 +/- 0.06 versus 1.4 +/- 0.03, P < .0001; mean +/- SEM), had significantly higher N-BNP levels (230 +/- 31 versus 121 +/- 10 pg/mL, P < .0001) and a more pronounced impairment of VO2peak (23.8 +/- 0.6 versus 28.4 +/- 0.5 mL x kg x min, P < .0001) than those without CI. Elevated odds ratios for CI were found in patients with a single ventricle (4.03), Mustard operation for transposition of the great arteries (3.11), and aortic coarctation (2.14). CONCLUSIONS: Our results indicate that CI in ACHD patients is a frequent problem and is related to the severity of the heart failure as measured by symptom assessment (New York Heart Association class), plasma N-BNP level and peak oxygen uptake.

Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery.

Heart failure (HF) is a major problem in the long-term follow-up of adults with congenital heart disease (CHD) after cardiac surgery. The purpose of this study was to evaluate risk factors for HF in patients with CHD. N-terminal-pro-brain natriuretic peptide and maximal oxygen uptake (VO2max) were measured in 345 consecutive patients with CHD. HF was defined as an elevated N-terminal-pro-brain natriuretic peptide level (> or = 100 pg/ml) and reduced VO2max (< or = 25 ml/kg/min). The HF criteria were met by 89 patients. These patients were significantly older (mean +/- SEM 30.8 +/- 0.9 vs 24.8 +/- 0.5 years), had significantly lower maximal heart rates (149 +/- 3 vs 164 +/- 1 beats/min), and had larger end-diastolic right ventricular diameters (36 +/- 1 vs 27 +/- 1 mm) and right ventricular pressure estimated by Doppler flow velocities of tricuspid valve regurgitation (2.9 +/- 0.1 vs 2.3 +/- 0.03 m/s). Mean fractional shortening of the left ventricle was within the normal range. To estimate risk stratification, odds ratios for HF were determined for the most frequently occurring types of congenital heart defects and surgical procedures. In conclusion, HF in adults with CHD predominately depends on diagnosis, age, the frequency of reoperation, and right ventricular function and may be related to chronotropic incompetence indicated by lower maximal heart rates.

Elevated brain natriuretic peptide and reduced exercise capacity in adult patients operated on for tetralogy of fallot is due to biventricular dysfunction as determined by the myocardial performance index.

Although tetralogy of Fallot (TOF) can be repaired surgically, residual lesions that cause abnormal ventricular load can eventually lead to heart failure. Subclinical biventricular dysfunction in these patients may be detected only by using suitably sensitive indexes. The Tei index determined by the pulsed Doppler method enables the measurement of left ventricular (LV) and right ventricular (RV) function. This study was designed to evaluate the biventricular Tei indexes in adults with operated congenital heart disease and to correlate these indexes with cardiopulmonary capacity and neurohormonal activation. Fifty-nine patients with surgically corrected TOF and 52 patients with operated left-to-right-shunt defects were included in the study. Patients with TOF showed significantly greater LV and RV Tei indexes than those with left-to-right-shunt defects (LV Tei index 0.50 +/- 0.09 vs 0.34 +/- 0.05, RV Tei index 0.37 +/- 0.1 vs 0.25 +/- 0.06; p <0.0001). Peak oxygen uptake was significantly reduced in the patients with TOF (25 +/- 6 vs 32 +/- 6 ml x kg(-1) x min(-1), p <0.0001) and was correlated inversely with the LV Tei index (r = -0.61, p <0.0001). N-terminal-pro-brain natriuretic peptide was significantly increased in patients with TOF (150 +/- 141 vs 57 +/- 39 pg/ml, p <0.0001). In conclusion, in asymptomatic or minimally symptomatic patients with TOF, biventricular dysfunction is detected by the Tei index. Further indexes for heart failure in these patients are increased circulating plasma N-terminal-pro-brain natriuretic peptide and impaired peak oxygen uptake. The combined determinations of these 3 variables enable the identification of congenital heart disease with impaired cardiac function before they become clinically symptomatic.

Relation of systemic ventricular function quantified by myocardial performance index (Tei) to cardiopulmonary exercise capacity in adults after Mustard procedure for transposition of the great arteries.

After Mustard repair for transposition of the great arteries, the right ventricle serves as a chronically overloaded systemic ventricle (SV). Thus, during long-term follow-up, dysfunction of the right ventricle with consecutive heart failure (HF) is not unusual. Early signs and symptoms of HF are depressed parameters of right ventricular (RV) function at rest and exercise intolerance. It was hypothesized that the measurement of RV function parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and peak oxygen uptake (VO2max) during exercise testing were suitable for the early detection of subclinical HF. In 33 asymptomatic adolescents and adults who had undergone Mustard repair, RV function was analyzed by the myocardial performance index (Tei index). NT-pro-BNP and VO2max were also determined. The corresponding data from 52 patients operated on for left-to-right shunt defects without residual lesions served as reference data. In patients who underwent the Mustard procedure, the Tei index and NT-pro-BNP were elevated (mean Tei index of the SV 0.63 +/- 0.17 vs 0.34 +/- 0.05, p <0.002; mean NT-pro-BNP 240 +/- 230 vs 57 +/- 39 pg/ml, p <0.0001), and VO2max was reduced (27 +/- 6 vs 32 +/- 6 ml x kg(-1) x min(-1), p <0.002). A good correlation was found between the Tei index and VO2max (r = -0.83, p <0.0001). In conclusion, RV function is depressed in most patients with Mustard repair. Ventricular dysfunction in such asymptomatic or minimally symptomatic patients can be detected by measurement of the Tei index, NT-pro-BNP, and VO2max. These parameters are simple and reliable screening methods to stratify patients with impaired cardiac dysfunction before they become symptomatic.

Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis).

OBJECTIVES: Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus concerning the postoperative mode and duration of anticoagulation prophylaxis. In a retrospective study, we evaluated the results of a prophylactic regimen on the basis of the surgical technique, potentially predisposing risk factors, and specific sequelae. METHODS: We evaluated 142 surviving patients after total cavopulmonary anastomosis (mean follow-up was 91.1 +/- 43.9 months). Prophylactic antithrombotic treatment was initiated in 86 patients with partial prosthetic venous pathway with acetylsalicylic acid; 45 patients with complete autologous tissue venous pathway or partial prosthetic venous pathway received no anticoagulation, and 11 patients received warfarin sodium (Coumadin). During long-term follow-up, 22 patients (12 after acetylsalicylic acid medication) crossed over to warfarin. RESULTS: Thrombotic events occurred in 10 patients (7%), with systemic venous thrombus formation in 8 (5.6%), stroke in 2 (1.4%), and a peak incidence during the first postoperative year. Eight of 10 patients were receiving heparin therapy mainly for prolonged postoperative immobilization. During follow-up, none of the 74 patients receiving acetylsalicylic acid and 1 of 40 patients without medication presented with thrombus formation. Under warfarin medication, 1 of 28 patients had an asymptomatic thrombus. Expected freedom from a thromboembolic event was 92% at 5 years and 79% at 10 years. There was no association with coagulation factor abnormalities. Protein-losing enteropathy was present in 4 of 10 patients. CONCLUSION: A prophylactic anticoagulation strategy that considers the surgical technique and potential predisposing circumstances proved effective in the prevention of late thrombotic complications after total cavopulmonary anastomosis. There is no need for routine anticoagulation during long-term follow-up after Fontan-type surgery in pediatric patients.

Plasma N-terminal pro-brain natriuretic peptide as a marker of right ventricular dysfunction in patients with tetralogy of Fallot after surgical repair.

OBJECTIVE: Chronic heart failure is associated with neurohormonal activation that is not only related to outcome but is also a therapeutic target. We have attempted to demonstrate whether a similar pattern of neurohormonal activation exists in adult congenital heart disease (ACHD) and, if so, whether it relates to disease severity determined by cardiopulmonary exercise testing. METHODS AND RESULTS: Concentrations of N-terminal pro-atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin (ET)-1, renin, aldosterone, adrenalin, and noradrenalin were determined in 50 adults (mean age, 27.8 +/- 1.7 years [+/- SEM]; 26 women) with tetralogy of Fallot (TOF) after surgical repair (New York Heart Association functional class 1.1 +/- 0.1). One hundred age- and sex-matched healthy blood donors served as a control group for NT-proBNP determination. Dimensions of ventricles, left ventricular pump function, and estimated right ventricular (RV) systolic pressure were determined by echocardiography. Maximum oxygen uptake (V(O2max) was measured in all patients using spiroergometry. TOF patients had elevated levels of NT-proBNP compared with healthy individuals: NT-proBNP (women: 180 pg/mL vs 43 pg/mL, and men: 147 pg/mL vs 32 pg/mL; p < 0.0001) and ET-1 (2.5 fmol/L vs 0.7 fmol/L). There was a significant correlation of NT-proBNP to dimension and estimated peak systolic pressure of the RV as well as impairment of V(O2max). CONCLUSIONS: RV dysfunction detected by echocardiography and plasma NT-proBNP determination in asymptomatic or minimally symptomatic TOF patients correlates well with their cardiopulmonary exercise capacity. Thus, these simple and noninvasive screening methods can be used additionally to stratify ACHD patients with impaired cardiac function before they become clinically symptomatic.

Normality of cardiopulmonary capacity in children operated on to correct congenital heart defects.

BACKGROUND: One of the main goals of corrective surgery of congenital heart defects in children is the improvement of quality of life, which in young children is predominantly determined by exercise capacity. It is not known whether this goal can be achieved in school-aged children who have undergone cardiac surgery in infancy. OBJECTIVES: To determine if primary school-aged children who underwent surgery to correct congenital heart defects in infancy are physically as fit as their peers. METHODS: We examined 84 children with congenital heart defects, aged 4 to 11 years, after surgical repair. Fifty-two children had simple defects (ie, atrial or ventricular septal defect, coarctation of the aorta). Thirty-two children had complex defects (ie, tetralogy of Fallot, pulmonary atresia with ventricular septal defect). All patients underwent exercise testing performed on a specially modified bicycle ergometer. Ninety-eight sex- and age-matched healthy children served as the control group. RESULTS: There was no gender difference, either in healthy children or in the group with congenital heart defects, regarding exercise testing and that the healthy children reached a mean +/- SD normalized maximal performance of 2.8 +/- 0.3 W/kg. The same range was found for the children who had undergone surgery to correct simple heart defects. The children operated on to correct complex heart defects showed significantly impaired mean normalized maximal performance, although this tended to be lower in the group that had pulmonary atresia with a ventricular septal defect than in the group with tetralogy of Fallot (mean normalized maximal performance, 1.9 W/kg vs 2.3 W/kg). CONCLUSIONS: The goal of normal exercise capacity in childhood after heart surgery is achieved in those with simple heart defects only. In children with complex heart defects impaired exercise performance persists, depending on the severity of the heart defect and probably on chronotropic incompetence.

Three-decade follow-up in pulmonary artery ectasia: risk assessment strategy.

We present a 29-year follow-up in a patient with ectasia of the pulmonary trunk and mild valvular stenosis. There was no progression from the first presentation at the age of 15 months until the actual age of 30 years, the z-value of the diameter of the pulmonary trunk remaining almost constant (z-value 22). This indicates that pulmonary dilatation with normal pressure may be a benign disease.

Cytokines in chronic heart failure: possible interaction in the neurohormonal and the cytokine system at the cAMP level?

In recent years, the pathophysiological concept of chronic heart failure (CHF) has changed from an isolated hemodynamic view to a more complex concept involving neuroendocrine and inflammatory pathways. New therapeutic strategies, such as beta-blocker therapy, are based on these new concepts and provide clinical evidence for a clinical benefit in patients with CHF. The survival benefit of beta-blocker therapy in CHF has been related to neurohumoral regulation. Thus, evidence evolved showing that following beta-blocker therapy cytokine levels in CHF patients are altered. We have shown that the levels of soluble TNF receptor type 2 correlated well with cAMP in leukocytes. Data from clinical studies in adult and infant CHF patients have demonstrated that beta-blocker therapy is accompanied by altered cytokine, cytokine antagonist, and/or soluble cytokine receptor levels. These alterations may result from a dysregulated interaction of beta-adrenergic pathways and the cytokine system, and are possibly related to cAMP-dependent regulation of the release or shedding of these mediators.

Acute pulmonary edema caused by epoprostenol infusion in a child with scimitar syndrome and pulmonary hypertension.

INTRODUCTION: Intravenous epoprostenol is frequently administered in adults and children for treatment of pulmonary hypertension. Although generally safe, pulmonary edema has been described in a few case reports of adult patients with pulmonary veno-occlusive disease. CASE REPORT: We present an infant who had an operation for scimitar syndrome and abnormal drainage of the right pulmonary veins into the inferior vena cava who developed pulmonary edema while receiving a prostacyclin infusion. The typical partial anomalous pulmonary venous drainage was operatively corrected at 6 days of age, and an accompanying coarctation was resected. At 7 months of age, diagnostic cardiac catheterization was performed to evaluate suspected pulmonary hypertension. Pulmonary pressure was elevated to supra-systemic values, and obstructed venous drainage of the right hypoplastic lung was demonstrated. To decrease pulmonary hypertension during weaning and extubation, epoprostenol infusion was initiated. Sixty minutes after extubation, massive acute pulmonary edema lead to reintubation. Mean airway pressure of 16 mm Hg (21 mbar) with pure oxygen ventilation was initially required, with an oxygenation index of 14, a ventilation index of 36, and an alveolar-arterial oxygen tension difference of 541 mm Hg. After discontinuation of epoprostenol, weaning and extubation was successful. CONCLUSION: Pulmonary edema caused by prostacyclin infusion in patients with impaired postcapillary pulmonary drainage may also be encountered in children and has to be anticipated.