Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach.

OBJECTIVE: Pregnancy in women with pulmonary hypertension (PH) is reported to carry a maternal mortality rate of 30-56%. We report our experience of the management of pregnancies using a strategy of early introduction of targeted pulmonary vascular therapy and early planned delivery under regional anaesthesia. DESIGN: Retrospective observational study. SETTING: Specialist quaternary referral pulmonary vascular unit. POPULATION: Nine women with PH who chose to proceed with ten pregnancies. METHODS: A retrospective review of the management of all women who chose to continue with their pregnancy in our unit during 2002-2009. MAIN OUTCOME MEASURES: Maternal and fetal survival. RESULTS: All women commenced nebulised targeted therapy at 8-34 weeks of gestation. Four women required additional treatment or conversion to intravenous prostanoid therapy. All women were delivered between 26 and 37 weeks of gestation. Delivery was by planned caesarean section in nine cases. All women received regional anaesthesia and were monitored during the peripartum period in a critical care setting. There was no maternal mortality during pregnancy and all infants were free from congenital abnormalities. One woman died 4 weeks after delivery following patient-initiated discontinuation of therapy. All remaining women and infants were alive after a median of 3.2 years (range, 0.8-6.5 years) of follow-up. CONCLUSION: Although the risk of mortality in pregnant women with PH remains significant, we describe improved outcomes in fully counselled women who chose to continue with pregnancy and were managed with a tailored multiprofessional approach involving early introduction of targeted therapy, early planned delivery and regional anaesthetic techniques.

The use of iloprost in early pregnancy in patients with pulmonary arterial hypertension.

In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.

Mechanical occlusion of the patent ductus arteriosus with Jackson coils.

The effectiveness and safety of a protocol for transcatheter patent ductus arteriosus (PDA) closure was assessed. Our goal is complete mechanical occlusion of the PDA in the catheterization laboratory by adding coils until it is no longer possible to cross the PDA with a guidewire. Detachable coil closure of a PDA with a narrowest diameter of 2.4 +/- 0.1 mm was attempted in 83 patients with a median age of 2.8 years (0.7 to 27.8 years) and whose median weight was 14.5 kg (6 to 61.6 kg). Coils were successfully implanted in 82 of 83 patients, and in 1 patient a large Rashkind double umbrella was used instead. Complete closure was obtained in 80 (97.6%) patients, 48 of those (59%) received more than one coil. Reintervention for residual shunting was required in only 1 patient and another patient has a trivial residual shunt. Device embolization occurred in three cases. Despite the use of multiple coils there was no evidence of significant left pulmonary artery stenosis. The fluoroscopy time increased from 14.0 +/- 2.0 minutes for a single coil to 25.3 +/- 2.9 minutes for multiple coils (p < 0.01). Attempting to obtain complete mechanical occlusion of the PDA during the implant procedure by adding extra coils reduces the need for reintervention for residual or recurrent shunting.

Left ventricular diastolic filling patterns associated with progressive anthracycline-induced myocardial damage: A prospective study.

The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m2 (median 270 mg/m2). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m2 of anthracycline. Six patients developed cardiac failure. After 1-100 mg/m2 of anthracyclines, the EA ratio decreased (mean 1.54-1.40, p = 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p = 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.

Left ventricular diastolic function in congenital myotonic dystrophy.

OBJECTIVE: Examination of left ventricular function and conduction abnormalities in myotonic dystrophy. DESIGN: Twelve patients (median age, 13.7 years) with myotonic dystrophy had detailed electrocardiography and echocardiography performed. Echocardiographic parameters were compared with body surface area (BSA) matched median normal values. RESULTS: Fractional shortening was slightly reduced (by 28-29%) in three patients and three patients had mild mitral valve prolapse. Diastolic function was abnormal; isovolumic relaxation time (IVRT) and duration of early filling were prolonged compared with control values (median IVRT, 74 v 61 ms). Peak E velocity was increased (median, 0.82 v 0.78 m/s) but atrial phase filling was normal. Heart rate was reduced (median, 68 v 81 beats/min). Conduction abnormalities were common but showed no clear relations with diastolic abnormalities. CONCLUSIONS: Young patients with myotonic dystrophy have myocardial diastolic dysfunction as well as abnormal electrophysiology. The prognostic implications of such abnormalities require further study.

Balloon expandable stents for systemic venous pathway stenosis late after Mustard's operation.

OBJECTIVES: Description and evaluation of current experience with the use of balloon expandable stents for the relief of systemic venous pathway stenosis late after Mustard's operation. DESIGN: Retrospective observational study of technical procedures, angiographic, and haemodynamic findings. PATIENTS: Twenty long term survivors of Mustard's operation for transposition of the great arteries (TGA) with angiographic evidence of systemic venous pathway narrowing. INTERVENTION: Systemic venous pathway stenoses were stented using balloon expandable Palmaz stents. RESULTS: Twenty seven stents were deployed across 24 stenoses. Seventeen stents were placed in the inferior baffle (16 patients), with an increase in mean (range) minimum diameter from 9.6 (4.5-15.9) to 16.5 (11.9-22.2) mm (p = 0.007), and a reduction in mean pressure gradient from 3.1 (0-8) to 0.67 (0-3) mm Hg (p = 0.002). Eight stents were placed in the superior pathways of eight patients, with diameters widened from 9.1 (3.5-14.1) to 15.2 (8.7-19.2) mm (p = 0.018), and gradients reduced from 6.4 (2-11) to 0.9 (0-2) mm Hg (p = 0.02). Two badly deployed stents were safely withdrawn from their intracardiac positions and redeployed in the iliac vein. Transvenous pacemaker insertion was facilitated by prior stent insertion. CONCLUSIONS: The use of balloon expandable stents for late systemic pathway narrowing after Mustard's operation is safe and effective. The beneficial effects of stenting are likely to be more durable than those of balloon angioplasty alone, but longer term follow up is required.

Transcatheter occlusion of the patent ductus arteriosus with Cook detachable coils.

OBJECTIVE: To report initial experience with a new occlusion device for native and residual patent ductus arteriosus. DESIGN: Descriptive study of consecutive non-randomised patients undergoing a new method of patent ductus arteriosus closure with detachable coils. SETTING: Tertiary centres for paediatric cardiology. PATIENTS: 71 consecutive patients, aged 1.2-22 years, with a patent ductus arteriosus (PDA) underwent elective transcatheter closure. 45 had native PDAs (group A) with a minimum diameter of 1.0 mm-5.0 mm (median 2.0 mm). A further 26 had undergone one or more previous occlusion attempts (group B). INTERVENTIONS: A total of 133 detachable (Cook) spring coils were successfully implanted in 70 patients. The procedure was performed transvenously in 51 patients, retrograde arterially in 13, and by both routes in a further 6 patients. One 5 mm coil migrated but was successfully retrieved. MAIN OUTCOME MEASURES: In group A colour flow Doppler echocardiography showed that complete occlusion was achieved in 40/45 (89%) at 24 hours, 41/45 (91%) at 1 month, and 44/45 (98%) by 6 months post procedure. Occlusion rates in residual PDAs were 22/25 (88%) occluded at 24 hours, 23/25 (92%) at 1 month, and 24/25 (96%) at 6 months follow up. CONCLUSIONS: Transcatheter occlusion using detachable (Cook) spring coils is a safe and effective alternative to presently available devices. The delivery system allows full retrieval of the coil until a satisfactory position is obtained.

Early identification of anthracycline cardiomyopathy: possibilities and implications.

The number of survivors of childhood cancer affected by anthracycline cardiomyopathy is steadily increasing, despite efforts to limit cardiotoxicity by dose restriction. Cardiac function was evaluated prospectively in 125 children during treatment to attempt to identify individual susceptibilities to cardiotoxicity and hence any potential for treatment modification. Left ventricular shortening fraction was used as an index of cardiotoxicity. Shortening fraction declined as cumulative anthracycline dose increased, at an average rate of 1% per 100 mg/m2. Six patients (5%) developed heart failure. Twenty four patients (19%) had abnormal shortening fraction (< 30%) by the end of treatment, and their rate of fall of shortening fraction was significantly steeper throughout treatment than in patients finishing with normal function (shortening fraction > or = 30%). This differential susceptibility to cardiotoxicity was apparent from very early in treatment, interquartile ranges of the two shortening fraction groups separating at doses > 200 mg/m2. Patients at high risk of risk of important anthracycline cardiotoxicity may be identifiable early in treatment by regular and careful monitoring of shortening fraction. However, frequent assessment is required and this has significant resource implications.

Surgery for infants with a hypoplastic systemic ventricle and severe outflow obstruction: early results with a modified Norwood procedure.

OBJECTIVE: Prospective audit of the first year of implementation of a modified approach to palliation for infants with hypoplastic systemic ventricle and severe systemic outflow obstruction. SETTING: Tertiary referral centre for neonatal and infant cardiac surgery. PATIENTS AND METHODS: 17 of 19 infants (aged < 35 days) presenting to Birmingham Children's Hospital in 1993 with hypoplastic systemic ventricle and severe outflow obstruction underwent surgery. This was performed using a new modification of the Norwood-type arch repair, without the use of exogenous material, and a 3.5 mm Gore-tex shunt between the innominate and right pulmonary arteries. The Gore-tex shunt was replaced by a cavopulmonary shunt between 3 and 5 months later. Clinical, morphological, and functional determinants of outcome were examined. RESULTS: 10 (59%) infants survived initial surgery. All proceeded to cavopulmonary shunt without further loss. Significant atrioventricular valve regurgitation seemed to be the main risk factor for poor outcome. If this was excluded, the morphology of the dominant ventricle seemed to have little effect on the outcome of initial surgery. CONCLUSIONS: Early survival was achieved in 59% of patients in the first year of implementation of a protocol for surgery in infants with hypoplastic systemic ventricle and severe outflow obstruction. The construction of a neoaorta without the use of exogenous material may allow improved later growth of the neoaorta. Early cavopulmonary shunt can be performed safely and should reduce mid-term complications from cyanosis and systemic ventricular volume loading.

Left ventricular diastolic function in children measured by Doppler echocardiography: normal values and relation with growth.

OBJECTIVES: To determine normal values for variables of left ventricular diastolic function in children measured by Doppler echocardiography and their relations to body surface area (BSA). BACKGROUND: There is increasing interest in echocardiographic assessment of left ventricular diastolic function in children but normal data for children are limited. METHODS: Assessment of left ventricular diastolic function was performed in 130 normal participants (aged from 2.4 months to 19.6 years) from their transmitral flow patterns obtained by pulsed wave Doppler echocardiography. RESULTS: Centile charts for commonly used left ventricular diastolic functional variables plotted against BSA are presented. Peak early diastolic filling velocity and atrial phase filling velocity integral were independent of BSA. Although most other filling indices showed strong relations with BSA, some had more curvilinear relations with BSA due to additional interactions with heart rate. The increase in left ventricular filling with growth is largely achieved by an increase in the early "passive" contribution to filling. The slower heart rates of older children are associated with lower atrial phase filling velocities but increased filling time, so the atrial contribution to filling remains relatively constant. CONCLUSIONS: Normal values of many left ventricular diastolic function variables change with growth in children and cannot be extrapolated from adult data. The data presented are suitable for use in size matched matched comparative studies of left ventricular function in children. Careful standardisation of echocardiographic protocols is necessary to ensure the validity of any comparisons.

Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology.

OBJECTIVES: To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. DESIGN: Cross sectional echocardiographic study of LV function. SETTING: Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. PATIENTS: 226 of 236 patients surviving between 6.5 months and 17 (median 5.3) years from initial anthracycline treatment for childhood malignancy attended for clinical and echocardiographic examination. Cumulative anthracycline doses were between 50 and 750 (median 300) mg/m2. 22 patients had also received cardiac irradiation. METHODS: Detailed assessment of transmitral diastolic pulsed wave Doppler flow patterns along with LV dimensions and systolic function measured by M mode echocardiography. MAIN OUTCOME MEASURES: Peak early (E) and atrial (A) phase filling velocities and EA ratio, time and acceleration and deceleration to and from peak E velocity, velocity integrals and ratio, isovolumic relaxation time (IVRT), and heart rate were measured. Results were examined in relation to LV cavity and posterior wall dimensions and shortening fraction (SF), and compared with paired control data matched for body surface area. RESULTS: Eleven (5%) patients had abnormal effort tolerance. Fifty one (23%) had SF < 30% and SF was inversely correlated with cumulative dose and time from treatment. The relative risk of symptomatic cardiac failure was greatly increased by prior irradiation; > 60% of irradiated patients who received > 400 mg/m2 of anthracycline were symptomatic. Early diastolic filling was relatively normal or enhanced at low anthracycline doses or when SF was preserved, with a shorter IVRT and increased atrial phase filling. Early filling was reduced at higher doses or with reduced SF, with longer IVRT and a further increase in atrial phase filling. A more "restrictive" pattern of diastolic filling (with high E and low A velocities) was seen in some patients, particularly after cardiac irradiation. CONCLUSIONS: Significant abnormalities of diastolic function are associated with anthracycline induced cardiac damage. These are not linearly related to anthracycline dose but appear to reflect the underlying myocardial pathophysiology associated with anthracycline toxicity, which is not demonstrated by the standard M mode echocardiogram. Although the overall clinical significance of such diastolic dysfunction is uncertain, some individual abnormalities may have significant management and therapeutic implications.

Cardiac involvement in seatbelt-related and direct sternal trauma: a prospective study and management implications.

The study set out to assess the incidence and consequences of pericardial and myocardial involvement in seatbelt-related sternal injury. Comparison was made with that from direct sternal trauma and implications for patient management were examined. The study was designed as a prospective sequential single centre study of 60 patients, from a total of 63 consecutive admissions over a 13 month period, admitted with blunt central chest trauma or multiple injuries involving the torso. Clinical status, correlated with echocardiographic, ECG and cardiac enzyme abnormalities were the main outcome measures. The study showed that 25% of 32 patients with seatbelt-related chest injury and 30% of 10 patients with multiple injuries had clinically unsuspected pericardial effusions detected by echocardiography. Pericardial effusion was not associated with an adverse outcome in the seatbelt-related injuries. Abnormalities of ECG or CK-MB isoenzyme levels were non-specific and did not correlate with the presence of pericardial effusion. From these data it is concluded that seatbelt-related sternal trauma is usually relatively benign. Echocardiography detects unsuspected pericardial effusion in a significant minority but ECG and cardiac enzyme estimations are of limited value. The routine admission to hospital of all patients with isolated seatbelt-related sternal trauma for cardiological monitoring is unnecessary. Inpatient treatment should be reserved for patients whose clinical condition, social circumstances or other injuries necessitate admission.

Mitral valve hypoplasia in children with isolated coarctation of the aorta.

OBJECTIVE: To test the hypothesis that isolated coarctation of the aorta is associated with relative hypoplasia of the mitral valve, even when the valve is morphologically normal. DESIGN: Cross sectional and Doppler echocardiography were used in a prospective, paired, case control study to compare mitral valve dimensions and diastolic transmitral flow characteristics as indices of left heart development. 40 children with isolated coarctation and 40 size matched controls were examined. Within the coarctation group 14 children with apical diastolic murmurs were compared with 14 size matched patients without murmurs. SETTING: A supraregional tertiary referral centre for paediatric cardiology. OUTCOME MEASURES: Mitral valve diameters, measured from the parasternal long axis, short axis, and apical four chamber views; mitral valve cross sectional area measured from the parasternal short axis view; peak early (E) and peak atrial (A) phase diastolic transmitral flow velocities measured by pulsed wave Doppler from the apical four chamber view; derived E/A ratio and pressure half time of decay from peak E. RESULTS: Mitral valve dimensions were significantly smaller in children with coarctation than in controls for long axis diameter (median 1.74 v 1.90cm, p = 0.0001), short axis diameter (2.21 v 2.28 cm, p = 0.027), and cross sectional area (2.37 v 3.15 cm2, p = 0.001). Peak E and A velocities were significantly higher in patients than in controls (0.9 v 0.82 ms-1, p = 0.013 and 0.61 v 0.51 ms-1, p = 0.007). The only difference between children with coarctation plus murmurs and those without murmurs was a marginally longer pressure half time. CONCLUSIONS: Smaller mitral valve dimensions and increased diastolic transmitral flow velocities in children with isolated coarctation compared with normal children suggests that coarctation may be part of a generalised hypoplasia of left heart structures.

Successful balloon dilatation of ascending vein stenosis in obstructed supracardiac total anomalous pulmonary venous connection.

A newborn infant presenting with severe hypoxia and pulmonary edema was found to have supracardiac total anomalous pulmonary venous connection (TAPVC). There was a severe localized stenosis (gradient > 30 mmHg) of the vein ascending from the pulmonary venous confluence. Balloon dilatation of the stenosis provided immediate and effective relief of the obstruction (gradient 4 mmHg) until surgery was performed. In sick neonates with discretely obstructed anomalous pulmonary venous connection, short-term hemodynamic stability may be achieved by balloon angioplasty of the site of obstruction.

Balloon dilatation (valvoplasty) as first line treatment for severe stenosis of the aortic valve in early infancy: medium term results and determinants of survival.

OBJECTIVE: To assess the results of balloon dilatation of the aortic valve as first line treatment for infants presenting in the first two months of life with cardiac failure caused by severe aortic stenosis. DESIGN: A prospective study of all such infants presenting to a single centre over a three year period. PATIENTS: Of 14 consecutive infants aged < 2 months presenting with heart failure due to severe stenosis of the aortic valve, 12 underwent balloon dilatation of the valve. Two infants with hypoplastic left heart syndrome were excluded. Six patients had other significant cardiac malformations, nine had endocardial fibroelastosis. Four infants were moribund at presentation. INTERVENTIONS: Balloon dilatation was performed through the femoral artery under general anaesthetic, with heparin and antibiotic prophylaxis. Maximum inflated balloon size was selected as equal to or slightly less than the diameter of the aortic valve measured echocardiographically. In two infants balloon dilatation of coexistent severe coarctation was performed at the same time. RESULTS: Dilatation was achieved in all cases. Early survival rate (up to one month) was 75%; 50% survive up to three years. The two deaths occurring < 24 hours after dilatation probably related to the infants' poor condition at presentation and the presence of significant left ventricular hypoplasia. The other early death was due to severe mitral regurgitation from papillary muscle dysfunction. All later deaths were related to associated malformations. The difference in left ventricular size (diameter and length) measured echocardiographically at presentation between survivors and those that died is significant (p < or = 0.002). 83% of deaths occurred in infants with associated malformations. Cusp perforation occurred in one infant, which may have contributed to this patient's death. Left ventricular perforation and cardiac tamponade were treated successfully by prompt pericardiocentesis in another. CONCLUSIONS: Balloon dilatation of the aortic valve is an acceptable first line treatment for neonates with severe symptomatic stenosis of the aortic valve. Outcome depends principally on left ventricular size and on the presence, severity, and timing of treatment of associated malformations. Severe endocardial fibroelastosis was not a risk factor for early death but may have implications for long term survival. The survival rate for this high risk group might be improved by a stratified approach where patients with adequate left ventricular size have balloon dilatation whereas those with severe ventricular hypoplasia are managed like patients with the hypoplastic left heart syndrome.

Cardioprotection by ICRF187 against high dose anthracycline toxicity in children with malignant disease.

OBJECTIVE: A pilot study to assess the efficacy of ICRF187 as a protective agent against the cardiotoxic effects of anthracycline drugs used to treat childhood malignancies. DESIGN: A study of cardiac function in children treated receiving ICRF187 ((s)-(+)-1,2 bis (3,5-dioxopiperazenyl) propane) in addition to anthracycline therapy compared with contemporary controls selected retrospectively on the basis of anthracycline dose matching. PATIENTS: Five children in whom recurrence of malignant disease was re-treated with chemotherapy containing anthracycline drugs and additional ICRF187 (supplied on a compassionate-use basis) (cumulative anthracycline doses 550-1650 mg/m2). Five more children with recurrence of malignant disease were re-treated to similar cumulative anthracycline doses (600-1150 mg/m2) without ICRF187. METHODS: Cardiac function was assessed clinically and echocardiographically throughout treatment. Clinical and echocardiographic state were compared before treatment and after completion of therapy within and between groups treated with and without ICRF187. RESULTS: Two patients treated without ICRF187 developed symptomatic congestive cardiac failure from which one died. Another developed considerable but as yet asymptomatic left ventricular dysfunction. No patient receiving additional ICRF187 developed cardiac failure or left ventricular dysfunction. There were no significant differences in cumulative anthracycline dose, dose increase, type of anthracycline used, survival rate, or length of survival between groups. Left ventricular shortening fraction fell by a mean of 1.0% in patients receiving ICRF187 and by a mean of 11% in the patients treated without it (p = 0.04). CONCLUSIONS: ICRF187 seems to have provided highly effective cardioprotection to this small group of children with end-stage malignancy. Severe cardiotoxicity was seen in a similar group treated with comparable anthracycline doses but without ICRF187.

Double partitioning of the left atrium: a previously unreported echocardiographic finding in a case in which transoesophageal echocardiography aided operative resection.

Precordial echocardiography showed two membranes obstructing pulmonary venous return in the left atrium of a 9 month old infant. This anomaly has not previously been described; therefore transoesophageal echocardiography was performed at the time of surgery. This confirmed the anatomy and aided complete resection of both membranes. Even in small infants transoesophageal echocardiography can provide useful information about complex atrial malformations.

Japanese B virus encephalitis in India--a growing problem.

Epidemic Japanese B Virus encephalitis is increasingly a major cause of mortality and morbidity in wide areas of SE Asia, but remains largely unknown to most western physicians. The very high incidence of permanent and disabling neurological sequelae has considerable socioeconomic impact. In view of the magnitude of the 1984 epidemic in India and the increasing possibility of the disease spreading to western countries, current knowledge of both epidemiological and clinicopathological features is reviewed, and illustrated by selected cases seen in a small hospital in NE India during the 1984 epidemic.