Systemic plasma vascular endothelial growth factor levels as a marker for increased angiogenesis during the single ventricle surgical pathway.

Cyanosis and the cavopulmonary anastomosis (CPA) are associated with pulmonary arterio-venous malformations (PAVMs) in single ventricle physiology. Vascular endothelial growth factor (VEGF) may be a marker of abnormal angiogenesis in this setting. Plasma VEGF levels were measured in 14 patients undergoing the surgical pathway leading to total cavopulmonary connection (TCPC). Venous blood samples were taken before and then months after CPA (n=6), and immediately before TCPC and 1 month thereafter (n=9). Corresponding arterial saturations were correlated with VEGF levels at each time frame. In six patients, pre-CPA plasma VEGF levels rose from a mean of 24.4-112.4 pg/ml (p<0.03) just prior to completion of TCPC. In nine patients, VEGF levels diminished from 115.7 to 48.9 pg/ml (p<0.05) after TCPC. VEGF levels were disproportionately elevated to arterial saturations most notably after CPA (r2=0.002), suggesting an additional angiogenic stimulus besides cyanosis. Plasma VEGF levels fluctuate during the single ventricle surgical pathway, with maximal levels after CPA, and regression after completion of TCPC. High VEGF levels are disproportionate to hypoxia after CPA, potentially incriminating the absence of hepatic flow to the lungs as an abnormal angiogenic stimulus. Measuring VEGF in venous blood may serve as a biochemical marker of angiogenesis after CPA.

Twenty-five years' experience with the arterial switch operation.

OBJECTIVE: The arterial switch operation was introduced in 1976 to correct transposition of the great arteries and has since replaced atrial palliation. This study examines the long-term outcomes of the arterial switch operation. METHODS: Included in the study were 195 patients who underwent the arterial switch operation from 1977 through June 2000. Patients were evaluated for functional class, pulmonary stenosis, left ventricular function, arrhythmias, aortic sequelae, and coronary disease. RESULTS: Overall perioperative mortality was 15%, but rates dropped in the last 5 years to 4% for complex transposition and 0% for simple transposition. Of 151 survivors, 2 died late; 1 died of persisting pulmonary hypertension and 1 died of ventricular fibrillation after coronary pathologic changes. At last follow-up, a total of 145 patients were in New York Heart Association functional class I and 4 patients were in class II. The most frequent complication was pulmonary stenosis, necessitating 45 reinterventions in 26 patients. Left ventricular dysfunction was noted in 5 patients. Arrhythmias were seen in 5 patients: 2 patients had ventricular fibrillation (1 died and 1 required a defibrillator implantation), 1 had sick sinus syndrome, 1 had atrial flutter, and 1 had a single attack of supraventricular tachycardia. Aortic valve incompetence was absent or trivial in 146 patients, 3 had mild incompetence, 1 had moderate incompetence, and 1 had severe incompetence. Coronary sequelae were found in 5 of the 61 patients who underwent angiography. CONCLUSION: Long-term clinical outcome of the arterial switch operation is good, and perioperative mortality is now low. Morbidity is dominated by pulmonary stenosis and coronary artery disease, with the potential for lethal arrhythmias.

Lactacidosis in the neonate is minimized by prenatal detection of congenital heart disease.

OBJECTIVES: To investigate the impact of prenatal detection of congenital heart disease on preventing severe preoperative lactacidosis. DESIGN: Patients operated upon for congenital heart disease during the first 31 days of life (n = 209) were studied retrospectively, 21 were diagnosed prenatally and 188 patients had not been diagnosed prenatally. Preoperative lactate, pH and base excess were evaluated. RESULTS: Differences were noted in preoperative pH (7.28 +/- 0.03 vs. 7.24 +/- 0.01, P = 0.29), base excess (-5.83 +/- 0.64 vs. -6.93 +/- 0.46 mmol/L, P = 0.10) and lactate (3.05 +/- 0.35 vs. 6.08 +/- 0.45 mmol/L, P < 0.001), indicating a significant difference in blood lactate values in favor of the prenatally diagnosed group. CONCLUSIONS: Prenatal diagnosis of congenital heart disease and the resulting immediate postnatal care prevent lactate increase in the preoperative period of these patients. This may decrease the risk of cerebral damage and result in the patient being in better condition at surgery.

Coronary artery fistulas.

The aetiology of congenital coronary artery fistulas remains a challenging issue. Coronary arteries with an anatomically normal origin may, for obscure reasons, terminate abnormally and communicate with different single or multiple cardiac chambers or great vessels. When this occurs, the angiographic morphological appearance may vary greatly from discrete channels to plexiform network of vessels. Coronary arteriovenous fistulas (CAVFs) have neither specific signs nor pathognomonic symptoms; the spectrum of clinical features varies considerably. The clinical presentation of symptomatic cases can include angina pectoris, myocardial infarction, fatigue, dyspnoea, CHF, SBE, ventricular and supraventricular tachyarrhythmias or even sudden cardiac death. CAVFs may, however, be a coincidental finding during diagnostic coronary angiography (CAG). CAG is considered the gold standard for diagnosing and delineating the morphological anatomy and pathway of CAVFs. There are various tailored therapeutic modalities for the wide spectrum of clinical manifestations of CAVFs, including conservative pharmacological strategy, percutaneous transluminal embolisation and surgical ligation.

Fate of the aortic root after arterial switch operation.

OBJECTIVE: Concerns have been voiced about possible dilation and insufficiency of the neo-aortic valve after the arterial switch operation (ASO). AIMS: To determine growth of the neo-aortic valve and the aortic anastomosis after ASO and the prevalence of insufficiency or stenosis. PATIENTS AND METHODS: Since 1977, 144 consecutive patients (pts) underwent ASO for transposition of the great arteries (TGA). Median follow-up was 8.65 years (0.1--22.5 years). Simple TGA was present in 97 pts and 47 had TGA with ventricular septal defect (VSD). Detailed echocardiography included measurements of aortic diameter at four levels. The 608 measurements were compared with published normal values. RESULTS: The mean aortic valve z-score was 1.5, without significant change with age (P=0.75). Under 4 months, mean valve z-score was 0.63+/-2.20, between 5 and 12 months 2.56+/-2.30 (P<0.0001). Gradual growth occurs thereafter. The aortic sinus follows an identical growth pattern. The aorta at the anastomosis, is initially smaller than normal (z-score -0.64). After 4 months the z-score is 0.83, followed by continued growth of 0.1 z-score per year. At the last visit, the aortic valve z-score was above 2 in 51 patients, between -2 and 2 in 72 and less than -2 in six patients, none of whom had a flow velocity above 2 m/s. z-score of patients with VSD remained above those without VSD (P<0.0001). Aortic insufficiency was grade 2/4 in three patients, grade 3/4 in one and grade 4/4 in one. No patient developed aortic stenosis. CONCLUSION: After ASO the neo-aortic valve and sinus are larger than normal, representing the natural size difference in the prenatal situation and influence of associated cardiac malformations. In the first year of life, rapid dilatation of the new aorta is observed, followed by growth towards normalization of the valve and sinus size. Stenosis at the anastomosis was not observed. Aortic dilatation by itself is rarely associated with significant insufficiency.

Aneurysmal pericardial patch producing right ventricular inflow obstruction.

A 2-month-old infant presented with acute onset of heart failure, having previously undergone anatomical repair of transposition of the great arteries and ventricular septal defect (VSD). Echocardiography demonstrated aneurysmal dilation of the native pericardial patch used for VSD closure, resulting in right ventricular inflow obstruction. The pericardial patch was excised, and the VSD closed using a GoreTex patch.

Prenatal diagnosis of congenital heart disease affects preoperative acidosis in the newborn patient.

OBJECTIVES: Congenital heart disease is the leading cause of death in the first year after birth. Prenatal diagnosis of the disease can optimize the preoperative condition of the patient and may help in the prevention of acidosis. In this retrospective study we compared the occurrence of metabolic acidosis in patients with and without prenatal diagnosis of a congenital heart disease. METHODS: Data of 408 patients who needed an operation for congenital heart disease within 31 days of life were analyzed retrospectively. Arterial blood gases at fixed time intervals and worst blood gas of 81 patients with and 327 patients without a prenatal diagnosis were compared, categorizing the patients on ductus dependency, anticipated univentricular or biventricular repair, and left-sided, right-sided, or no heart obstruction. RESULTS: In the overall group significant differences in lowest pH, lowest base excess, and highest lactate level were found, with metabolic acidosis more common among the patients with a postnatal diagnosis. In the group of patients with ductus-dependent congenital heart disease, the difference between patients receiving a prenatal and those receiving a postnatal diagnosis was more significant than in the group with non-ductus-dependent lesions. Analyzing patients with right-sided, left-sided, and no obstruction separately, significant differences were found in the group with left-sided heart obstruction for lowest pH and base excess and in the group with right-sided heart obstruction for lowest base excess. CONCLUSIONS: Prenatal diagnosis of congenital heart disease minimizes metabolic acidosis in patients with congenital heart disease and may be associated with improved long-term outcome and prevention of cerebral damage among this fragile group of patients, although no significant effect on direct surgical outcome was encountered.

[Surgical treatment of hypoplastic left heart syndrome: limited success]. / De operatieve behandeling van het hypoplastisch linkerhartsyndroom: beperkt succes.

OBJECTIVE: To inventory the treatment of hypoplastic left heart syndrome (HLHS) in the Netherlands and its results. DESIGN: Retrospective. METHOD: Data were collected from all patients (n = 117) diagnosed with HLHS in the Wilhelmina Children's Hospital-University Medical Center Utrecht and the University Hospital Rotterdam-Sophia Children's Hospital and born in the period 1 March 1988-31 May 2000. Type and time of intervention, and mortality were recorded and cumulative survival was analysed by Kaplan-Meier analysis. Cumulative survival was compared between early and late series and between the two hospitals. RESULTS: The study group comprised 68 boys and 49 girls, all neonates. At the time of the investigation, the mean duration of follow-up was 185 days (range: 0-3855). Fifty-eight children had received no treatment; all of these had died. Fifty-nine children were scheduled for the Norwood procedure; six of them died before operation. The 53 patients who underwent the first stage of the Norwood procedure had 1-month, 1-year, 2-year, and 5-year survival chances of 55%, 30%, 27%, and 24% respectively. Survival chances between the two time periods and the two hospitals showed no significant differences. CONCLUSION: The Norwood procedure was performed in almost half of the children with HLHS. It is only moderately successful; however, it seems the only realistic choice in the management.

[Arterial-switch operation for transposition of the great vessels; good results in the Wilhelmina Children's Hospital, Utrecht, 1977-2000]. / Arteriële-switchoperatie bij transpositie van de grote vaten; gunstige resultaten in het Wilhelmina Kinderziekenhuis Utrecht, 1977-2000.

OBJECTIVE: To examine the results of the arterial switch operation which is used to correct the transposition of the great arteries. DESIGN: Descriptive. METHOD: In the period May 1977-October 2000 195 patients at the Wilhelmina Children's Hospital in Utrecht, the Netherlands, underwent an arterial switch operation. The patient group consisted of 132 boys and 63 girls, with a median age at surgery of 8 days (range: 0-1976). In accordance with the protocol, the postoperative follow-up consisted of echocardiography and an ECG. Further investigations were performed on indication. Additional data were collected from the status reports. The mean follow-up was 8.0 years (range: 0.04-22.17). RESULTS: The overall peri-operative mortality was 15% (30/195). Initially this figure was about 50%, in the 1980s it was 15% and from 1996 onwards it was 4%. Of the 151 surviving and traceable patients, 2 patients died years later (1.3%). Of the remaining 149 patients, 145 were classified in New York Heart Association class I and 4 in class II. Due to pulmonary stenosis, 45 reinterventions were required in 26 patients (/149; 17%). Left ventricle dysfunction occurred in 5 patients (3%), arrhythmias in 5 patients and aorta abnormalities in 5 patients. Coronary artery abnormalities were found in 5 of the 61 patients who underwent angiography (8%). CONCLUSION: Peri-operative mortality decreased to 4% and late mortality was 1.3%. The long-term clinical outcome of the arterial switch operation was good. Morbidity was predominantly caused by pulmonary stenosis and late coronary obstruction.

Right ventricular dysfunction and the role of pulmonary valve replacement after correction of tetralogy of Fallot.

BACKGROUND: Correction of tetralogy of Fallot (ToF) often leads to pulmonary regurgitation, sometimes warranting pulmonary valve replacement (PVR), for which the indications and timing to achieve optimal results are not yet clear. This retrospective study describes follow-up and reinterventions in our ToF population. METHODS: Review of all consecutive patients operated for ToF between 1977 and 2000. Included are date and type of repair, Doppler echocardiography (2D-echo), ECGs, re-operations and physical condition. RESULTS: Total repair was performed in 270 patients, mean age 1.9±2.5 years, 82 were excluded because of follow-up abroad. Right ventriculotomy was used in 92%, transatrial VSD closure in 8%, while 69% received a transannular outflow patch. Pulmonary atresia required a pulmonary graft in 13 (8%) patients. Overall 20-year survival was 88%. Last follow-up: ECG showed RBBB in 67% (QRS complex 129±29.3 msec). RVOT aneurysms were detected in 16%. 2D-echo demonstrated mild pulmonary insufficiency (PI) in 40%, severe in 31%, dilated RV in 76%, both increasing with post-repair age. In 39%, RV dimensions were equal or even exceeded LV dimensions, 45% showed tricuspid insufficiency and the RA was enlarged in 14%. Reintervention was necessary in 39/185 patients, this included angioplasty for residual stenosis and PVR (22/19 homografts, six patients in PA group) at a mean age of 11.2 years after correction. In seven patients, the RV returned to normal dimensions and symptoms disappeared, but in three severe dysfunction developed. Eleven others still have RV dilatation and/or PI. In total, 75% were free of reintervention in the first ten years. The right atrial approach diminishes severe RV dilatation and prolonged QRS duration (p=0.001 and 0.007). Early correction reduces the risk of re-operation (p=0.011). CONCLUSIONS: Severe RV dilatation (39%) and PI (31%) secondary to outflow tract repair in ToF are frequently occurring sequels developing slowly over time. Timing of PVR remains controversial, still best guided by the clinical condition.

[Balloon angioplasty as the primary treatment for coarctation of the aorta in 30 children; immediate results and follow-up]. / Ballonangioplastiek als primaire behandeling van coarctatio aortae bij 30 kinderen; directe resultaten en follow-up.

OBJECTIVE: Evaluation of the results of balloon dilatation in coarctation of the aorta in children. DESIGN: Retrospective. METHOD: In the years 1990-1999 30 patients with a congenital coarctation of the aorta were treated with balloon angioplasty in the Children's Heart Centre of Utrecht University Medical Centre, the Netherlands. The group comprised 5 girls and 25 boys, with a mean age of 4.8 years (range 1 month-16 years) without severe associated congenital heart defects or a long segment coarctation. Follow-up included Doppler echocardiography and MRI within the first 6 years after the procedure. The fall of the pressure gradient was assessed with Student's t-test for paired observations and the reintervention period was calculated by the Kaplan-Meier method. RESULTS: No children died. Of 30 procedures performed, 28 (93%) were considered successful. Mean pressure gradient was reduced from 36.2 mmHg (SD: 12.7) to 13.1 mmHg (SD: 9.3) (p < 0.001). Mean follow-up was 4.1 years; the follow-up of 11 patients was longer than 5 years. Four patients (13%) developed a recoarctation. No aneurysm formation was encountered (n = 14). CONCLUSION: Balloon angioplasty for the treatment of native coarctation of the aorta in children may be an efficient and not very damaging solution for this selected group of patients.

Influence of coronary anatomy and reimplantation on the long-term outcome of the arterial switch.

BACKGROUND: Abnormal coronary artery anatomy is reported to have a significant influence on the outcome of the arterial switch operation. This study examines the impact of coronary anatomy and the occurrence of late coronary obstruction on left ventricular (LV) function and long-term outcome. METHODS: Coronary artery anatomy, of 170 patients after arterial switch operation (1977-1999), was determined based on operative reports and pre-operative aortograms. Current status was evaluated using ECGs, echocardiograms, scintigraphy, and post-operative coronary angiograms. RESULTS: In 133/170 patients, coronary artery anatomy consisted of an anterior descending (LAD) and circumflex artery (Cx) from the left sinus and the right coronary artery (RCA) from the right or posterior sinus. The left coronary had an intramural initial course in two of these patients. Fifteen patients had the LAD from the left and Cx and RCA from the right sinus; eight had LAD and RCA from one sinus and Cx from the other; four had single ostium; and three had three separate ostia. Four patients had complex patterns and four patients had a supra commissural coronary. To date, follow-up angiography was performed in 59 patients. Surgical coronary sequellae were found in five patients. Two patients had an occluded left ostium. Initially, they were asymptomatic but showed polymorphic ventricular extrasystoles on ECG and moderate LV dysfunction with large irreversible perfusion defects on scintigraphy. Both patients developed ventricular fibrillation at the age of 14 years. One patient did not survive. The other patient required implantation of a defibrillator. One patient has an occluded RCA, one patient has stenosis of the right ostium and one patient has multiple tortuous collaterals without obstruction of a major branch. In the latter three patients, coronary sequellae were not suspected on ECG, echo, or scintigraphy and were only found on follow-up angiography. Retrograde collateral flow was noted in all three occluded coronaries. LV dysfunction, with normal coronaries, was noted in three patients. All, of these patients, had peri-operative ischaemia suggesting failure of myocardial protection. Two are now asymptomatic with mild LV dysfunction. One patient continues to have severe myocardial dysfunction and secondary aortic insufficiency. A Ross-like procedure was performed placing the original aortic valve in the neo-aortic root. Coronary artery anatomy did not influence early survival or late coronary sequellae. CONCLUSION: Abnormal coronary anatomy was not a determinant of outcome in our study. Surgical coronary obstruction is independent of original anatomy. It can be almost silent and is potentially fatal. Follow-up angiography must be considered in all patients after the arterial switch operation.

[Heart transplantation in the Netherlands, an option to be considered for 5 children per year on the average]. / Harttransplantatie in Nederland; een te overwegen optie voor gemiddeld 5 kinderen per jaar.

OBJECTIVE: To assess the number of possible candidates for paediatric cardiac transplantation and the number of available donors. DESIGN: Retrospective. PATIENTS AND METHODS: The population (date of birth 1 January 1980-31 March 1998) of the Department of Paediatric Cardiology of the Wilhelmina Children's Hospital, Utrecht, the Netherlands, was reviewed for possible candidates for cardiac transplantation and the resulting number of candidates was extrapolated to the entire country. Figures of the transplant co-ordination unit of the University Hospital Utrecht over 1993-1997 were obtained, to estimate the number of available donors. Furthermore, an overview was made of the results of paediatric cardiac transplantations reported in centres around the world. RESULTS: A total number of 15 possible candidates could be selected over the studied period. Extrapolated to the entire country, about 5 candidates each year could be expected. Per year 5 donor hearts of children (< 12 yr) and 11 hearts of adult donors with a low body weight (40-65 kg) have been available for paediatric cardiac transplantation. Worldwide 5- and 10-year survival rates reach 60% and 50%, respectively, morbidity seems low and the quality of life can be considered reasonably good. CONCLUSION: The number of expected recipients corresponds with the number of available donors. Together with the promising results reported in transplant centres around the world, this seems to justify the option of paediatric cardiac transplantation for children with end-stage cardiac disease.

Tetralogy of Fallot with absent pulmonary valve. A continuing challenge.

Absent pulmonary valve syndrome (APVS); the combination of tetralogy of Fallot (TOF) with agenesis of the pulmonary valve, is a relatively rare cardiac malformation. Despite the anatomic similarity with classic TOF, the pathophysiology is strikingly different. Data on 10 patients (3 male, 7 female) with APVS, treated between January 1978 and December 1995, were retrospectively reviewed. During this period a total of 2920 children underwent correction of a variety of congenital cardiac anomalies, of which 246 patients (8%) had a correction for TOF. Two patients with APVS presented within the first four months of life with severe cardiorespiratory distress and required several operative procedures. The remaining eight patients had only mild to moderate respiratory and/or cardiac symptoms and elective intracardiac repair was performed on those between the ages of 10 months and 9.5 years. Associated cardiac anomalies seen in five patients included aberrant coronary artery, absent or interrupted left pulmonary artery, partial AVSD and aberrant azygos continuation. In those electively corrected, the strategies used were ventriculotomy (7), pulmonary homograft (3) and aneurysmorrhaphy (2). There were two deaths, one in each group of patients, as a result of progressive respiratory insufficiency and cardiac tamponade, respectively. The follow-up of the eight survivors ranged from 2 to 11 years (median 6.75). All have a normal effort tolerance; only one child is on digoxin therapy, and one child continues to suffer bronchospastis episodes. Our experience with infants with this lesion is limited but underlines the different approaches required, depending on the age of presentation.