Low-dose anthracyclines in childhood Acute Lymphoblastic Leukemia (ALL): no cardiac deterioration more than 20 years post-treatment.

INTRODUCTION: In children with cancer a well-known risk factor for cardiotoxicity is a high cumulative dose of anthracyclines, but little is known about cardiac function in low-dose anthracycline-treated survivors. Also, it is unclear if a safe anthracycline-dose exists at all. PATIENTS AND METHODS: Cardiac function was assessed in 23 long-term ALL-survivors with a median follow-up of 22 years (range 19.5-24.5) post-treatment. Age at diagnosis and current age were 5.0 (2.0-14.0) and 29.0 (24.0-39.0) years. All 23 survivors were treated according to DCLSG protocol ALL-5, including 18-25 Gy cranial irradiation. Thirteen of them received 4 x 25 mg/m(2) daunorubicin by randomization. Cardiac evaluation included blood pressure measurement, echocardiography, and (24 h-) electrocardiogram. Results were compared with an earlier assessment at median 12 years post-treatment. RESULTS: None of the survivors had cardiac abnormalities. Cardiac status of daunorubicin-treated survivors showed no deterioration compared with the previous assessment in 1995. CONCLUSION AND IMPLICATION FOR CANCER SURVIVORS: After prolonged follow-up (more than 20 years post-treatment), ALL-survivors treated with low dose daunorubicin had no clinical relevant deterioration of cardiac function.

Long-term cardiac follow-up in survivors of a malignant bone tumour.

BACKGROUND: Longitudinal studies of cardiac function in long-term childhood cancer survivors are scarce and frequently concern a median follow-up shorter than 13 years. PATIENTS AND METHODS: Cardiac assessment was performed in 22 doxorubicin-treated long-term survivors of a malignant bone tumour at median 22 years (range 15-27.5) post-treatment. Age at follow-up was 39 years (range 27-59) and cumulative dose of doxorubicin was 360 mg/m(2) (range 225-550). Cardiac function was assessed by echocardiography and (24-h) ECG. The results were compared with those of earlier assessments at 9 years (1992) and 14 years (1997) post-treatment. RESULTS: Systolic dysfunction was found in 27% (9% in 1997; P = 0.02) and diastolic dysfunction in 45% (18% in 1997; P = 0.02). Heart rate variability showed further deterioration compared with earlier results. CONCLUSIONS: Twenty-two years after doxorubicin-treatment, bone tumour survivors showed progressive cardiac dysfunction.

Cardiac status in bone tumor survivors up to nearly 19 years after treatment with doxorubicin: a longitudinal study.

BACKGROUND: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. PROCEDURES: Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] RESULTS: We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. CONCLUSIONS: Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.

The role of echocardiography in transcatheter closure of atrial septal defects.

Closure of so-called "secundum" atrial septal defects with a device inserted on a catheter necessitates precise delineation of their morphology. Echocardiography is the diagnostic method of choice to demonstrate this morphology, and to differentiate such defects located within the oval fossa from the other variants producing an interatrial communication. Precordial echocardiography usually allows selection of cases likely to be suitable for closure in this fashion. This selection is based on the localisation and the size of the deficiency in the oval fossa, the length of the interatrial septum, and the adequacy of the infolded rims surrounding the defect. Suitability for closure is reevaluated by transesophageal echocardiography, either as a separate investigation or at the start of the interventional catheterisation. This investigation requires a multiplane transesophageal echocardiographic probe, since only oblique planes will demonstrate the entrance of the systemic and pulmonary veins and their relationship to the defect. Transesophageal echocardiography serves as an important monitoring tool during the interventional procedure. As such, it is a necessary adjunct to fluoroscopy. The stretched diameter of the defect measured with a balloon is the main determinant of the choice of the type and size of the device. This diameter can be measured fluoroscopically, as well as on echo. Colorflow mapping serves to rule out residual shunting during the occlusion of the defect with the balloon. During deployment of the device, constant echocardiographic visualisation of the device and its position relative to the atrial septum facilitates proper placement. Such constant visualisation can only be provided by repeated quick acquisitions of multiple planes. Once the device is released, the investigator should continue to record the position of the device, and assess the potential for residual shunting. Most of the devices show some subtle change in position during the first 20 minutes after implantation.

A European multicentric experience using the CardioSEal and Starflex double umbrella devices to close interatrial communications holes within the oval fossa.

In this review, we describe the experience from 13 European centres using the CardioSEAL and Starflex double umbrella devices to close interatrial communications within the oval fossa (so-called 'secundum' defects). Between October 1996 and April 1999, the procedure was attempted in 334 patients with a mean age of 12 years and a mean weight of 44kg. The mean measured stretched diameter of the defect was 15 mm. In the overall group, the defect was solitary in 245 patients (73%), multiple in 21 (6%), associated with an aneurysm of the flap valve in 15 (5 %), was represented by patency of the oval foramen in 44 (13%), and was a fenestration in a Fontan repair in 9 (3%). In all patients, the devices were inserted under general anesthesia, using fluoroscopic and transesophageal echocardiographic control. Implantation was achieved in 325 (97,3%). The device embolized within either a few minutes or a few hours in 13 patients (4%). Of these, uncomplicated surgical repair was undertaken in 10, while the device was retrieved in 3 using catheters and a second device was successfully implanted. Residual shunting was detected immediately after the procedure in 41% of the patients, with the incidence decreasing to 31% at discharge, 24% at 1 month, 21% at 6 months, and 20.5% at one year. During the period of follow-up, elective surgical repair became necessary in two patients, due to malposition of the device in one, and late embolization in the other. Fractures of arms were seen in 6.1 %, most commonly with the largest devices. All those with fractured arms of the device were asymptomatic, and no clinical complications related to the fractures were observed. There were no arrhythmias, endocarditis, valvar distortion, thromboembolic events, or other complications. After one year of follow-up, clinical success, defined as complete closure of the defect or presence of only a trivial leak, had been obtained in 92.5% of the patients. We conclude, therefore, that these devices produce excellent results when used to close defects of small to moderate size. Results are less than optimal, or else complications ensure, when attempts are made to close very large defects.

Pseudoaneurysm of the left ventricle after isolated pericarditis and Staphylococcus aureus septicemia.

Left ventricular pseudoaneurysm after isolated pericarditis as a result of Staphylococcal septicemia is very rare. A case of a very young patient is described. Diagnosis is made by echocardiography. Immediate surgical resection of the pseudoaneurysm is the therapy of choice.

The right auricle tunnel as intercaval tunnel in total cavopulmonary connection may prevent atrial flutter.

OBJECTIVE: Total cavopulmonary connection (TCPC) is a routine operation for palliation of children with cardiac anomalies in whom biventricular repair is impossible. The original technique consists of the creation of a semi-prosthetic intercaval tunnel. A substantial proportion of these patients develop atrial flutter. We developed a technique for creating an intercaval tunnel that uses the tissue of the right auricle as intercaval tunnel. This technique avoids suture lines in the neighbourhood of the blood supply of the sinus node and leaves the terminal crest free. Since atrial flutter frequently occurs after Mustard and Senning operations in which suture lines are similar as for creating the lateral tunnel in TCPC we postulated that our technique for creating the intercaval tunnel without prosthetic material might prevent atrial flutter. METHODS: All the children that qualified for a TCPC were included. Whenever possible our operative technique was applied. In the other cases a semi-prosthetic conduit was used for creating the intercaval tunnel. Of 47 consecutive patients 30 (64%) had a tunnel of right auricle tissue, 12 (26%) had a tunnel of prosthetic material. Five patients did not need an intercaval tunnel and were omitted in this study. Only surviving patients were included in this study. Patients that needed more atrial surgery then necessary for TCPC were also omitted. Postoperative ECG's and Holter monitorings were studied. RESULTS: Overall mortality was 7 of 47 patients (14.9% 70% CL 9.4-22.2%). There was no mortality due to rhythm disturbances. Atrial flutter occurred in 3 of 31 included patients (9.7, 70% CL 4.3-18.5%). In the right auricle group 1 of 22 patients (4.5, 70% CL 0.6-14.6%) had atrial flutter compared to 2 of 9 patients (22.2, 70% CL 7.5-45.0%) in the prosthesis group (P=0.13). CONCLUSION: The use of the right auricular technique for creating the intercaval tunnel TCPC is applicable in the majority of patients qualifying for a TCPC. Mortality and morbidity are equal comparing the two techniques. However, markedly less atrial flutter occurs in the group where the right auricle was used as intercaval tunnel. Therefore, we recommend the use of our technique for total cavopulmonary connection.

Late cardiotoxicity after treatment for a malignant bone tumor.

Cardiac function was assessed in long-term survivors of malignant bone tumors who were treated according to Rosen's T5 or T10 protocol, both including doxorubicin. Thirty-one patients, age 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of treatment. Cumulative doses of doxorubicin were 225-550 mg/m2 (median dose 360). The evaluation consisted of a history, physical examination, electrocardiogram (ECG), signal averaged ECG, 24-hour ambulatory ECG, echocardiography and radionuclide angiography. Eighteen of 31 (58%) patients showed cardiac toxicity, defined as having one or more of the following abnormalities: late potentials, complex ventricular arrhythmias, left ventricular dilation, decreased shortening fraction, or decreased ejection fraction. The incidence of cardiac abnormalities increased with length of follow-up (P< or = .05). No correlation could be demonstrated between cumulative dose of doxorubicin and cardiac status, except for heart rate variability. When adjusted to body surface area, the left ventricular posterior wall thickness (LVPW index) was decreased in all patients. The incidence of doxorubicin-induced cardiotoxicity is high and increases with follow-up, irrespective of cumulative dose. Life-long cardiac follow-up in these patients is warranted. The results of our study suggest that heart rate variability and LVPW index could be sensitive indicators for cardiotoxicity.

Decision making for the surgical management of aortic coarctation associated with ventricular septal defect.

Coarctation of the aorta and associated ventricular septal defect may be repaired simultaneously or by initial coarctation repair with or without banding of the pulmonary artery. The question is whether specific preoperative criteria can enable the surgeon to choose the optimal surgical management. Between 1980 and 1993, 80 infants younger than 3 months with coarctation and ventricular septal defect were treated surgically. In 64 infants (multistage group), simple coarctation repair was performed through a posterolateral approach, with concomitant banding of the pulmonary artery in 10 infants. Twenty ventricular septal defects were closed as a secondary procedure and four were closed as a tertiary procedure. Sixteen infants (single-stage group) underwent one-stage repair through an anterior midline approach. The total in-hospital mortality rate was 7.5%. Freedom from recoarctation after 5 years was 91.3% in the multistage group versus 60.0% in the single-stage group (p = 0.018). Freedom from secondary ventricular septal defect treatment in the multistage group after 5 years was 40.7%, versus 100% in the single-stage group (p = 0.016). Thirty-seven ventricular septal defects (47.8%) closed spontaneously. In particular, the preoperative left-to-right shunt and extension of the perimembranous VSD into the inlet or outlet were risk factors for the need for eventual surgical ventricular septal defect closure after initial coarctation repair. On the basis of these two risk factors, the probability of the need for eventual surgical treatment of ventricular septal defect after initial coarctation repair can be calculated. This policy offers a well-considered choice between single-stage and multistage repair, weighing the risk of secondary ventricular septal defect treatment versus the risk of recoarctation. Finally, the number of surgical procedures per infant will be as low as possible.

Aspirin versus indomethacin treatment of patent ductus arteriosus in preterm infants with respiratory distress syndrome.

Indomethacin (Indo) is commonly used for treatment of patent ductus arteriosus (PDA) but has renal failure as a main side effect. Aspirin (ASA) is an alternative, but there are no controlled trials on its efficacy. We randomly assigned 75 premature infants suffering from respiratory distress syndrome (RDS) (mean gestational age: 29.6 +/- 2.5 wk, mean birth weight: 1295 +/- 464 g) (+/- SD) and on artificial ventilation at the start of the study (mean: 3.4 d of life), to either Indo (3 x 0.2 mg/kg/12 h) or ASA (4 x 15 mg/kg/6 h). PDA and degree of shunting were evaluated by echocardio-Doppler; side effects were carefully recorded. PDA closed in 35/38 patients from the Indo group (92%) and in 16/37 patients from the ASA group (43%) (p < 0.0001). Nineteen patients needed further treatment with Indo or surgery (17 in the ASA group and 2 in the Indo group). The only side effect observed was a decrease of uresis in the Indo group during 4 d post treatment (p < 0.01). Closing of PDA was positively correlated with gestational age, but not with time of starting Indo/ASA or grade of shunting. We conclude that ASA is not as effective in closing PDA as Indo, but has no adverse effect on uresis.

The restricted surgical relevance of morphologic criteria to classify systemic-pulmonary collateral arteries in pulmonary atresia with ventricular septal defect.

Now that systemic-pulmonary collateral arteries are used for unifocalization in patients with pulmonary atresia and ventricular septal defect, the question arises whether morphologic criteria of these collateral arteries could help to provide better results. In an attempt to classify the morphologic features of systemic-pulmonary collateral arteries, we studied 31 heart-lung autopsy specimens with pulmonary atresia and ventricular septal defect. The course of the systemic-pulmonary collateral arteries (origin, branching pattern, and connections with systemic and central pulmonary arteries) was related to their histologic characteristics. The results show that systemic-pulmonary collateral arteries cannot be classified according to their course related to the trachea and the main branches of the bronchi. The histologic features of these collateral arteries vary along their course to the lungs. Nearly all systemic-pulmonary collateral arteries contain a muscular or a musculoelastic segment. One type of collateral artery (complex loop anastomoses) is completely muscular and resembles a bronchial artery. Nutritive branches (bronchial arteries) arise from all histologic types of systemic-pulmonary collateral artery segments. The size and number of intimal proliferations in muscular, elastic, and musculoelastic segments did not differ significantly. In 29 of 31 cases a ductus arteriosus did not coexist with large collateral arteries (two cases unknown). It is concluded that a classification of large systemic-pulmonary collateral arteries based on morphologic features results in a highly variable system, which does not facilitate decisions for the suitability of these arteries for unifocalization procedures. The variability of the systemic-pulmonary collateral arteries corresponds with the recent embryologic finding that during development, collateral artery formation is possible during extended periods.

Hypertrophic obstructive cardiomyopathy as a side effect of dexamethasone treatment for bronchopulmonary dysplasia.

We report three infants who developed hypertrophic obstructive cardiomyopathy during dexamethasone treatment for bronchopulmonary dysplasia. In all three infants, echocardiography had ruled out cardiac abnormalities prior to the dexamethasone course. The hypertrophic obstructive cardiomyopathy appeared and progressed during dexamethasone therapy and resolved completely after its cessation. This suggests a causative association between the hypertrophic obstructive cardiomyopathy and the exogenous glucocorticosteroid therapy. The mechanism of this dexamethasone-related hypertrophic obstructive cardiomyopathy is unclear. This complication may be encountered more frequently with the increasing use of dexamethasone in infants with bronchopulmonary dysplasia.

The value of transesophageal echocardiography in children with congenital heart disease.

With the use of dedicated pediatric single-plane probes, transesophageal echocardiography was performed prospectively in 102 children to determine the potential value of this new technique in the diagnosis (40 patients) and the follow-up of congenital heart disease (29 patients) and as a monitoring technique during the perioperative period or interventional cardiac catheterization (33 patients). The findings were correlated with precordial studies (102 patients), cardiac catheterization (82 patients), epicardial ultrasound findings (18 patients), or surgical inspection (34 patients). The age at investigation ranged from 2.5 months to 14.9 years (mean age, 5.2 years); weight ranged from 3.7 to 52 kg (mean weight, 19.1 kg). Additional information was obtained in 49 patients (48.4%) and was relevant for patient management in 21 patients (20.6%). Major areas of improved diagnostic insight included the following: (1) systemic and pulmonary venous return, (2) atrial morphology, (3) atrioventricular junction abnormalities, (4) left ventricular outflow tract disease, (5) atrial baffle function, and (6) the Fontan circulation. Inherent limitations were as follows: (1) the semiinvasive character of the procedure, (2) the need for heavy sedation or general anesthesia, and (3) the limited imaging planes provided. Transesophageal echocardiography in children can provide important additional diagnostic information on a wide spectrum of congenital heart lesions. The technique would appear to be a highly valuable adjunct to the diagnostic armentarium of the pediatric cardiologist.

Assessment of ventricular septal defect closure by intraoperative epicardial ultrasound.

Intraoperative epicardial two-dimensional echocardiographic imaging, color flow mapping and contrast echocardiography were used in 31 patients after patch closure of a ventricular septal defect to determine their respective values in the assessment of residual shunting after cardiopulmonary bypass and for the prediction of long-term results. Epicardial imaging showed no incidence of patch dehiscence. Residual shunting detected by color flow mapping or contrast echocardiography was graded into one of four categories (0 to III). Real time analysis of color flow mapping studies suggested no shunting (grade 0) in 2 patients, grade I shunting in 20, grade II in 8 and grade III in 1; contrast studies suggested grade 0 in 15, grade I in 6, grade II in 8 and grade III in 2. Interobserver variation in real time encoding of grade I or II shunting was 25% by color flow mapping and 6% by contrast echocardiography. Subsequent frame by frame analysis revealed that both diastolic and early systolic right ventricular turbulence gave rise to false positive results during real time analysis of color flow mapping studies. Color flow mapping allowed exact localization of residual shunting, whereas contrast echocardiography allowed better semiquantification. Postbypass results were correlated in 30 patients with late postoperative precordial studies (mean interval 7.5 months). Persistent shunts were found in 6 (20%) of 30 patients. No patient required reoperation for residual shunting. The predictive value of immediate grade I or II shunting as a marker for persistent long-term shunting was poor, whereas both patients with immediate grade III shunting had shunt persistence, indicating that immediate revision should be considered in such patients. Intraoperative epicardial ultrasound is valuable for the immediate exclusion of important residual shunting after ventricular septal defect closure. Maximal information is obtained when color flow mapping and contrast echocardiography are used in combination.

Comparative values of the precordial and transesophageal approaches in the echocardiographic evaluation of atrial baffle function after an atrial correction procedure.

Previous methods used to assess atrial baffle function after correction of transposition of the great arteries have included precordial echocardiography and cardiac catheterization. To evaluate whether single plane transesophageal echocardiography might provide additional information, its findings were correlated with information derived from both precordial echocardiography and cardiac catheterization in 15 patients (14 Mustard procedures, 1 Senning procedure) aged 4.2 to 33 years (mean 16.3). Precordial ultrasound with combined imaging, color flow mapping and pulsed Doppler ultrasound visualized the supramitral portion of the common systemic venous atrium in every case but could identify only superior limb obstruction in three of six patients, mid-baffle obstruction in zero of two and inferior limb obstruction in zero of two patients. Transesophageal studies with use of the same range of ultrasound methods demonstrated superior limb obstruction (severe in four, mild in two) in six of six patients, mid-baffle obstruction in two of two and inferior limb obstruction in two of two patients. The entire pulmonary venous atrium was equally well interrogated by either ultrasound approach, with both identifying three cases (two mild, one moderate) of mid-pulmonary venous atrium obstruction. However, individual pulmonary vein velocity profiles could only be recorded by transesophageal pulsed Doppler ultrasound. Precordial studies identified baffle leaks (1 large, 2 small) in only three patients, whereas transesophageal studies identified 11 such baffle leaks (1 large, 10 small), which were multiple in two patients. It is concluded that transesophageal echocardiography provides a more detailed and accurate assessment of atrial baffle morphology and function than is provided by either precordial ultrasound or cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Juxtaductal pulmonary artery coarctation. An underestimated cause of branch pulmonary artery stenosis in patients with pulmonary atresia or stenosis and a ventricular septal defect.

An angiographic and clinical study was performed to establish the prevalence of juxtaductal pulmonary artery coarctations in patients with pulmonary atresia or stenosis and a ventricular septal defect or a complex intracardiac defect. The present study is an adjunct to a previously reported portmortem study, in which the incidence of these pulmonary artery coarctations was found to be unexpectedly high. Pulmonary artery coarctations were identified angiographically in 10 of the 15 patients with pulmonary atresia. One additional patient had a bilateral ductus arteriosus and confluent pulmonary arteries, but did not have a pulmonary artery coarctation. Pulmonary artery coarctations were much less prevalent in the cases with pulmonary stenosis (5/50). However, these pulmonary artery coarctations appeared identical to those of the cases with pulmonary atresia. Fourteen pulmonary artery coarctations were located in the pulmonary artery at the side of the ductus arteriosus; this was left sided in 12 and right sided in two patients. In one patient the side of the ductus could not be established. The types and the locations of the pulmonary artery coarctations in the present study were identical to those in the previous postmortem study. Ductal tissue was found in many of the pulmonary artery coarctations of the postmortem study and is likely to be present in the clinical cases as well. The majority of the angiographically identified pulmonary artery coarctations were subsequently confirmed at operation or at autopsy. The clinical outcome and follow-up of the patients is discussed, and it is concluded that juxtaductal pulmonary artery coarctations should be specifically looked for before and during any type of surgical intervention in these patients.