Philip Rees

Lung transplantation and life extension in children with cystic fibrosis.

BACKGROUND Lung transplantation has been available as therapy for end-stage lung disease since the early 1980s, but survival after transplantation remains poor, with continued controversy as to the survival benefit from the procedure. We examined the effect of lung or heart-lung transplantation on the survival of a cohort of children with cystic fibrosis and severe lung disease. METHODS Between May, 1988, and May, 1998, 124 children with cystic fibrosis were accepted for lung transplantation. 47 received transplants, 68 died while they awaited organs, and nine remained on the active waiting list. We constructed a proportional-hazards model that used variables of prognostic significance in this population. By including transplant status as a time-dependent covariate, we were able to calculate a hazard ratio for transplantation. Date of entry into the study was the date when children were added to the list for transplantation, and measurements were taken at this time. Children were accepted for transplantation if they had a life expectancy of 2 years or less, a poor quality of life, and no contraindications to transplantation. FINDINGS After 1 year, 35 (74%) children were still alive; after 5 years 12 (33%) children were alive. The univariate hazard ratio for transplantation was 0.41 (95% CI 0.23-0.74; p=0.003). Transplantation remained significantly associated with survival after correction for differences in age, sex, height-corrected forced expiratory volume in 1 s, minimum oxygen saturation during a 12 min walk, haemoglobin concentration, albumin concentration, and age-corrected resting heart rate (hazard ratio 0.31 [0.13-0.72]; p=0.007). INTERPRETATION If centres follow our criteria for accepting patients for transplantation, and achieve similar survival after transplantation, they could expect a survival benefit for their patients in line with our results.

Percutaneous balloon valvuloplasty for pulmonary valve stenosis in infants and children.

Pulmonary valve stenosis was relieved by balloon dilatation during cardiac catheterisation on 27 occasions in 23 infants and children aged 7 days to 12 years, median 31 months (three aged less than 2 weeks). Pulmonary valve diameter was estimated by cross sectional echocardiography to assist in the choice of balloon size. Before dilatation the right ventricular systolic pressure ranged from 41 to 190 (median 92) mm Hg and was suprasystemic in 10 patients. There were significant reductions in the ratio of right ventricular to systemic systolic pressure and pulmonary systolic pressure gradients immediately after balloon dilatation. Twelve patients underwent recatheterisation (11 at six months and one at one week after balloon dilatation), which showed further improvement with significant reductions in right ventricular pressure or pulmonary valve gradient or both, particularly in the patients with the least satisfactory initial results. This improvement was attributed to resolution of the obstruction at infundibular level. Repeat pulmonary valve dilatation was successfully performed in four patients who had poor results after initial dilatation. Balloon pulmonary valvotomy appears to provide good short term and medium term relief of pulmonary valve stenosis and may obviate the need for surgery in many cases. An apparently poor immediate haemodynamic result does not preclude a good longer term result.

Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Effect of systemic pulmonary anastomosis.

In nine patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, the effect of a systemic-pulmonary anastomosis on the lung was studied by comparison of pre- and postoperative cine angiograms. Selective injections into the collateral arteries were performed in all patients and the source of blood supply to each bronchopulmonary segment was sought. Central pulmonary arteries were present in six children and absent in three, as confirmed at thoracotomy. After insertion of a shunt, central pulmonary arteries increased in size, but the intrapulmonary vessels with which they connected remained abnormally small and were frequently stenosed. In addition, in each case the central pulmonary arteries increased flow to only five to 11 segments of lung. In the absence of central pulmonary arteries, shunting to a hilar or a lobar pulmonary artery increased perfusion to five to nine segments of lung per case. In all these three cases the pulmonary arteries at lobar level showed aneurysmal dilatation proximal to a severe stenosis. Sixty-eight per cent of collateral arteries were stenosed. The findings suggest that in this anomaly, when the central pulmonary arteries are hypoplastic, the intrapulmonary branches are also hypoplastic, emphasising the need for early surgical intervention to increase blood flow while the lung still has growth potential. Further, one collateral artery may connect with at least as many bronchopulmonary segments as does a central pulmonary artery, and the peripheral intrapulmonary arteries with which it connects may appear at least as normal angiographically as do vessels connected to central pulmonary arteries. These observations suggest that segments of lung connected to collaterals alone should, and sometimes can, be connected to central pulmonary arteries, the aim being to produce a unifocal blood supply as a prelude to total correction.

Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children

Background— Cytomegalovirus (CMV) infection has been implicated as a cause of posttransplantation coronary artery disease in adults. The purpose of this retrospective observational study was to evaluate the effect of CMV on outcome after heart transplantation in children. Methods and Results— Risk factors tested were recipient age, sex, and pretransplantation CMV serology; use of anti-CMV prophylaxis; posttransplantation evidence of CMV infection; and donor CMV serology. Transplantations were stratified traditionally according to CMV risk as low risk (recipient negative/donor negative), intermediate risk (recipient positive), and high risk (recipient negative/donor positive). Primary outcome measures were (1) development of coronary artery vasculopathy, (2) mortality (or graft loss) that occurred outside the early postoperative period, and (3) death (or graft loss) due to vasculopathy. Analysis was by proportional hazards modeling. A total of 165 children underwent heart transplantation, with a mean age at transplantation of 7.8 (SD 5.6) years. Thirty-two children had laboratory evidence of CMV infection after transplantation, but only 6 developed CMV disease or syndrome. Traditional CMV risk stratification correlated well with CMV infection but did not predict mortality, coronary artery disease, or coronary death. In contrast, positive recipient CMV was the only independent predictor of all 3 outcome measures: coronary artery disease (hazard ratio=3.6), all-cause mortality (partial hazard ratio=4.1), and coronary death (hazard ratio=4.6). Conclusions— In children, pretransplantation recipient CMV status is a more powerful predictor for the development of clinically significant vasculopathy and subsequent death than traditional risk stratification. This phenomenon warrants further investigation.

Infective endocarditis in children with congenital heart disease: comparison of selected features in patients with surgical correction or palliation and those without.

The diagnostic and prognostic features of 44 episodes of infective endocarditis in 42 children with congenital heart disease were reviewed. Endocarditis occurred in 18 patients who had not had surgical correction or palliation of the defect (non-operated group). There were 26 episodes in 24 patients who had been treated surgically (operated group) (16 open and eight closed cardiac operations). Endocarditis occurred soon after open heart surgery in eight patients and as a late complication in the other 16. It recurred in two patients (operated group). Invasive monitoring and low cardiac output were consistent features in those patients who had endocarditis soon after open heart surgery whereas dental treatment was a common feature in non-operated cases and after closed cardiac operations. Late cases of endocarditis after open heart surgery had various microbiological features that were not typical of infection after dental problems. Gram positive infections occurred in non-operated patients and in those who had had closed cardiac operations. The group that had open heart surgery had infections caused by Gram positive, Gram negative, and anaerobic bacteria and fungi. Fever, anaemia, leucocytosis, and positive blood cultures were the only consistent findings. Vegetations were seen in nine of 12 patients at cross sectional echocardiography. All 12 (four non-operated, one closed, and seven open cases) needed acute surgical treatment. The mortality from infective endocarditis was 17% for non-operated cases, 0% for those who had had closed heart surgery, and 50% for those who had had open heart surgery. Infective endocarditis after open heart surgery differs from that in the other subgroups in terms of microbiology, source of infection, and outcome and its early diagnosis depends on a thorough investigation of minimal symptoms and signs.

Univentricular heart of right ventricular type with double or common inlet.

Seventeen cases are described in which both atria connect directly to a chamber with right ventricular characteristics. The atria connected through separate atrioventricular valves in six hearts and a common valve in 11. All hearts had a posterior rudimentary chamber. The septum which separated it from the main chamber was directed to the crux of the heart. Ten hearts were from patients with atrial situs solitus and seven from patients with atrial situs ambiguus. Arterial connections were concordant in three cases, had a double outlet from the main ventricular chamber in nine and single outlet of the heart in five. The patent artery always arose from the main chamber, with pulmonary atresia in three and aortic atresia in two. This and other studies indicate that double inlet atrioventricular connection does not predict the morphology of the main chamber. Although usually associated with a main chamber of left ventricular type, it may also be associated with a main chamber having right ventricular characteristics. Both types should be considered as univentricular hearts; the posterior chamber in hearts of right ventricular type are analogous to the anterior chamber in univentricular hearts of left ventricular type and are a rudimentary chamber rather than a hypoplastic ventricle. In the right ventricular form of univentricular heart, the trabecular zone of the rudimentary chamber is of left ventricular type

Heart and heart–lung transplantation for idiopathic restrictive cardiomyopathy in children

Objective: To review the outcome of cardiac transplantation for restrictive cardiomyopathy (RCM) in children and to assess the ability of new strategies to modulate the effects of high pulmonary vascular resistance. Design: Retrospective case note analysis of all patients receiving a transplant for RCM. Patients: 18 children with RCM referred for transplantation assessment to Great Ormond Street Hospital, London. Results: Eight boys and 10 girls were referred for assessment. Median age at presentation was 5.0 (mean (SD) 6.1 (4.0)) years. Fourteen orthotopic and two heterotopic transplantations were performed and two patients were referred for heart–lung transplantation. Mean duration from diagnosis to transplantation was 3.3 (3.0) years. Three patients with haemodynamic decompensation before transplantation had increased morbidity in the postoperative period. No patients died while awaiting a transplant. Three patients died in the first year after transplantation, one within 30 days. Five patients received pre-transplantation prostacyclin for a mean duration of 57 (18) days. Transpulmonary gradient was reduced in four of the patients. Mean transpulmonary gradient was 27 (9.8) mm Hg before and 17 (6.7) mm Hg after treatment with prostacyclin (p < 0.05). Conclusion: Most children with RCM require transplantation within four years of diagnosis. Referral for transplantation assessment should precede haemodynamic decompensation. Increase of pulmonary vascular resistance is a variable problem but can be modulated with pre-transplantation prostacyclin. With these strategies, orthotopic transplantation is possible in the majority of cases.

Balloon dilatation of the aortic valve for congenital aortic stenosis in childhood.

Balloon dilatation of the aortic valve was attempted in 34 consecutive children aged 16 months to 17 years (median 7 years), weight range 9-60 (median 22) kg. Previous surgical valvotomy had been performed in two patients (twice in one of them). The valve was not crossed in one patient. In the remaining 33 patients the pressure difference between the left ventricle and the ascending aorta during systole was reduced from 71 (30) to 28 (19) mm Hg. In 24 patients recatheterisation 2-19 (mean 9) months later showed gradients that were similar to those immediately after balloon dilatation (35 (20) v 31 (20) mm Hg). The two patients with the highest residual gradients immediately after balloon dilatation showed a spontaneous reduction in gradient at repeat catheterisation, whereas the patient who had twice had previous surgical valvotomy showed an increase in gradient from 37 to 99 mm Hg over nine months and required aortic root replacement. Balloon dilatation was repeated in two patients and this caused a further reduction in gradient. New aortic regurgitation occurred in nine (27%) patients (grade I, 8; grade II, 1) and aortic regurgitation was exacerbated (grade I to II) in two of the nine with pre-existing aortic regurgitation. External iliac artery avulsion occurred in one (3%) patient and two (6%) required intravenous streptokinase because the femoral artery became occluded. There were no other complications. Open valvotomy was performed in the child in whom the valve was not crossed, but no other child required aortic valve operation. Balloon dilatation of the aortic valve gave reasonable short term palliation and was well tolerated. It is an alternative to surgical valvotomy for initial palliation of congenital aortic stenosis in many children.

Results of heart-lung transplantation in children with cystic fibrosis

Children with cystic fibrosis represent the largest group referred for, and undergoing, heart-lung transplantation at our institute. Between June 1988 and July 1993, 76 patients were accepted for transplantation, of whom 25 were transplanted, while a further 36 died waiting. Those transplanted ranged from 5-18 years of age and included 13 males and 12 females. Organs were used from donors matched by ABO blood group, size and cytomegalovirus (CMV) status. Post-transplant maintenance immunosuppression comprised cyclosporin A, azathioprine and prednisolone. Anti-thymocyte globulin and high dose methylprednisolone were given peri-operatively and for acute rejection episodes. Actuarial survival was 67% at 1 year, 61% at 2 years and 54% at 3 years. Obliterative bronchiolitis (OB) has occurred in 13 patients (52%) and was the major cause of mortality and morbidity. In three patients, OB was associated with the development of tracheal anastomotic stenosis. Other complications included diabetes mellitus (n = 9), pancreatitis (n = 1) and hypertension (n = 8). Despite these problems, those surviving the first year post-transplant showed a mean FEV1 of 71% (compared to 29% pre-transplant) and enjoyed an overall improved quality of life.

Successful cardiac transplantation in Barth syndrome - : single-centre experience of four patients

Abstract:  We describe four patients with Barth syndrome who have undergone successful orthotopic heart transplantation. Patients are one, seven, 12.5 and 14.7 yr post‐transplantation. One episode of severe infection occurred. Renal dysfunction and coronary allograft vasculopathy do not appear accelerated over non‐Barth patients. Despite withholding purine synthesis inhibitors, these patients have not demonstrated an increased rate of rejection.