Anthony P. Salmon

Hepatic changes in the failing Fontan circulation

Background: The failing Fontan circulation is associated with hepatic impairment. The nature of this liver injury is poorly defined. Objective: To establish the gross and histological liver changes of patients with Fontan circulation relative to clinical, biochemical and haemodynamic findings. Methods: Patients were retrospectively assessed for extracardiac Fontan conversion between September 2003 and June 2005, according to an established clinical protocol. Twelve patients, mean age 24.6 (range 15.8–43.4) years were identified. The mean duration since the initial Fontan procedure was 14.1 (range 6.9–26.4) years. Results: Zonal enhancement of the liver (4/12) on CT was more common in patients with lower hepatic vein pressures (p = 0.007), and in those with absent cardiac cirrhosis on histological examination (p = 0.033). Gastro-oesophageal varices (4/12) were more common in patients with higher hepatic vein pressure (21 (6.3) vs 12.2 (2.2) mm Hg, p = 0.013) and associated with more advanced cirrhosis (p = 0.037). The extent of cirrhosis (7/12) was positively correlated with the hepatic vein pressure (r = 0.83, p = 0.003). A significant positive correlation was found between the Fontan duration and the degree of hepatic fibrosis (r = 0.75, p = 0.013), as well as presence of broad scars (r = 0.71, p = 0.021). Protein-losing enteropathy (5/12) occurred more frequently in patients with longer Fontan duration (11.7 (3.2) vs 17.9 (6.1) years, p = 0.038). Conclusions: Liver injury, which can be extensive in this patient group, is related to Fontan duration and hepatic vein pressures. CT scan assists non-invasive assessment. Cardiac cirrhosis with the risk of developing gastro-oesophageal varices and regenerative liver nodules, a precursor to hepatocellular carcinoma, is common in this patient group.

Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: A three-year prospective study

OBJECTIVES To assess the incidence of microdeletions of chromosomal region 22q11 in a population of infants coming to a regional pediatric cardiac center with selected abnormalities of the ventricular outflow tracts and aortic arch and, further, to provide phenotypic/genetic correlations to determine whether patients with 22q11 deletions can be clinically recognized in infancy. BACKGROUND DiGeorge syndrome and velocardiofacial syndrome are frequently associated with malformations of the ventricular outflow tracts and aortic arch. Both are usually caused by microdeletions of chromosomal region 22q11. The overall importance of such deletions as a cause of these cardiac malformations remains to be established. STUDY DESIGN All infants with the candidate cardiac phenotypes during a 34-month period were studied. Dysmorphic features, type of cardiac defect, serum calcium concentration, and thymic status were recorded. Cytogenetic studies, including high-resolution karyotyping and fluorescence in situ hybridization using cosmids (cEO or cH748) from the DiGeorge critical region, were performed after clinical assessment. RESULTS Fifty infants (including 36 with tetralogy of Fallot with or without pulmonary atresia) were seen during the study period. Twenty-six infants (52%) were dysmorphic, including 19 who were considered to have a phenotypic appearance consistent with 22q11 deletion. Genetic analysis confirmed hemizygosity for 22q11 in 8 of these 19 cases. Results of fluorescence in situ hybridization studies were normal in 22 infants without dysmorphic features and in 5 infants with dysmorphic features not suggestive of a 22q11 deletion. CONCLUSIONS Microdeletions of chromosomal region 22q11 are an important cause of selected malformations of the ventricular outflow tracts and aortic arch and account for about 15% to 20% of cases. These deletions may be clinically recognized in early infancy and can be rapidly confirmed by fluorescence in situ hybridization.

Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study

Aims: To describe the histological features of the liver in patients with a Fontan circulation. Methods: Specimens from liver biopsies carried out as part of preoperative assessment prior to extracardiac cavopulmonary conversion of an older style Fontan were examined and scored semi-quantitatively for pertinent histological features. To support the use of the scoring, biopsy specimens were also ranked by eye for severity to allow correlation with assigned scores. Results: Liver biopsy specimens from 18 patients with a Fontan circulation were assessed. All specimens showed sinusoidal fibrosis. In 17 cases there was at least fibrous spur formation, with 14 showing bridging fibrosis and 2 showing frank cirrhosis. In 17 cases at least some of the dense or sinusoidal fibrosis was orcein positive, although a larger proportion of the dense fibrous bands were orcein positive compared with the sinusoidal component. All specimens showed marked sinusoidal dilatation, and 14 showed bile ductular proliferation; 1 showed minimal iron deposition, and 1 showed mild lobular lymphocytic inflammation. There was no cholestasis or evidence of hepatocellular damage. Similar appearances were observed in 2 patients with severe tricuspid regurgitation. Discussion: The histological features of the liver in patients with a Fontan circulation are similar to those described in cardiac sclerosis. Sinusoidal dilatation and sinusoidal fibrosis are marked in the Fontan series. The presence of a significant amount of orcein negative sinusoidal fibrosis suggests there may be a remediable component, although the dense fibrous bands are predominantly orcein positive, suggesting chronicity and permanence. No inflammation or hepatocellular damage is evident, suggesting that fibrosis may be mediated by a non-inflammatory mechanism.

Electrophysiological Mapping and Ablation of Intra-Atrial Reentry Tachycardia After Fontan Surgery With the Use of a Noncontact Mapping System

BACKGROUND Atrial tachyarrhythmias are a complication of Fontan surgery. Conventional electrophysiological mapping and ablation techniques are limited by the complex anatomic and surgical substrate and a high arrhythmia recurrence rate. This study investigates the use of noncontact mapping to identify arrhythmia circuits and guide ablation in Fontan patients. METHODS AND RESULTS Eleven arrhythmias were recorded in 6 patients. Noncontact mapping improved recognition of the anatomic and surgical substrate and identified exit sites from zones of slow conduction in all clinical arrhythmias. Radiofrequency linear lesions were targeted across these critical zones in 5 patients. One patient underwent surgical cryotherapy. Although immediate success was achieved in 3 of 5 patients with radiofrequency ablation, 2 patients had a recurrence after a mean of 6.4 months of follow-up. The patient who underwent cryoablation remains free of arrhythmias. CONCLUSIONS Noncontact mapping can identify arrhythmia circuits in the Fontan atrium and guide placement of ablation lesions. Arrhythmia recurrence is high, possibly because of inadequate lesion creation rather than inaccurate mapping and lesion targeting.

Outcome after repair of tetralogy of Fallot in the first year of life

BACKGROUND The purpose of this study was to evaluate the early and late outcome after repair of tetralogy of Fallot in the first year of life. METHODS Between 1974 and 2000, 89 consecutive infants with a mean age of 6.3 +/- 2.6 months (range, 15 days to 12 months) underwent repair of tetralogy of Fallot (ventricular septal defect and pulmonary stenosis) by one surgeon (J.L.M.). Three infants had previous palliative operations. Sixty-seven procedures were urgent or emergency. A transannular patch was inserted in 69 patients (77.5%). Follow-up was complete, averaging 13.4 +/- 5.6 years (range, 0 to 25.4 years). RESULTS There was one operative death (1.1%). Mean right ventricular to left ventricular pressure ratio postoperatively was 0.4 +/- 1.1 (in 79 patients, < 0.5). Fourteen patients underwent reoperations or reinterventions. There were no reoperations for residual or recurrent ventricular septal defect. Kaplan-Meier freedom from reoperation or reintervention for any cause at 20 years was 85% +/- 4.4%, for relief of right ventricular outflow tract obstruction it was 94% +/- 3.1%, and for pulmonary valve replacement this was 95.4% +/- 2.6%. Use of a transannular patch did not significantly affect the need for reoperation or reintervention. There was one late death (leukemia). Kaplan-Meier 20-year survival was 97.8% +/- 1.9%. On latest echocardiography, 42 patients had moderate pulmonary regurgitation, 4 had a right ventricular outflow tract gradient more than 40 mm Hg, and 86 had good biventricular function. Twelve-lead electrocardiography was performed in all and 24-hour electrocardiography in 61 patients. One patient (1.1%) exhibited late recurrent ventricular tachycardia requiring implantation of a defibrillator. The remaining 86 patients are in New York Heart Association class I with none of them receiving antiarrhythmic medications. CONCLUSIONS These data strongly support the concept of early repair of tetralogy of Fallot. It is associated with an acceptable operative risk and a low incidence of significant arrhythmias, and provides long-term survival similar to that observed in the general population. Late complications may, however, develop, and long-term follow-up for their early recognition is essential.

Twelve year experience with the modified Blalock-Taussig shunt in neonates

Between 1978 and 1990, 53 consecutive modified Blalock-Taussig (MBT) shunts were performed on 51 neonates with cyanotic congenital heart disease using 3 mm-5 mm Gore-Tex grafts. Only 4 of these children had uncomplicated tetralogy of Fallot. The remainder had more complicated pathology requiring urgent intervention. Retrospective analysis of the acute and long term results was performed with 100% follow-up, ranging from 1 month to 12 years (mean 3 years). There were 3 (6%) early deaths (within 30 days of operation) and 17 (33%) late deaths. Of the late deaths, 2 died after further palliation, 2 died after total correction and 13 died suddenly at home. Post mortem examination of the 13 sudden deaths revealed blocked shunts in only 3. Actuarial survival at 2 years was 58%. Shunt patency at 12 months was 87% and at 2 years, 62%. No patient used their initial MBT shunt for more than 40 months. Although this shunt provides good initial palliation, there is a high incidence of late sudden death. We are also concerned about the limited life span of the shunt which partly (3/13) explains the sudden deaths. Therefore we have adopted an aggressive approach to re-study by angiography within 3 months of surgery.

Mitral valve replacement with mechanical prostheses in children: improved operative risk and survival.

OBJECTIVE The purpose of this study was to assess the early and late outcome following mitral valve replacement (MVR) with mechanical prostheses in children. PATIENTS AND METHODS Between 1981 and 2000, 44 consecutive children (mean age 6.8+/-4.7 years, 2 months--16 years) underwent mechanical MVR in Southampton. Twenty-three children were less than 5-years-old and nine were infants. Disease aetiology was congenital in 37, rheumatic in four, infective in two and Marfans syndrome in one. Mitral regurgitation was present in 36 and mitral stenosis in eight. Concomitant procedures were performed in 13, including aortic valve replacement (AVR) in seven. Follow-up was complete (mean 6.4+/-4.8 years, 1 month--18.1 years). RESULTS The overall operative mortality was 14% (six patients). Before and after 1990 operative mortality was 31 vs 3.6% (P=0.02). From 1990, operative mortality for infants was zero out of six, for children less than 5-years-old was one out of 16 (one death after emergency AVR and MVR) and for older children it was 0/12. Seven children experienced valve or anticoagulation treatment-related events and eight had a mitral valve re-operation. Ten-year freedom from thromboembolism, prosthetic valve infection, bleeding, paravalvular leak and a mitral valve re-operation was 92.8+/-5.2, 97.3+/-2.7, 97.7+/-2.3, 97.2+/-2.7 and 75+/-9.7%, respectively. Overall 10-year survival was 78+/-7% (four late deaths); for children under vs over 5 years it was 61+/-11 vs 95.2+/-4.6% (P=0.02), for atrio-ventricular septal defect (AVSD) vs other pathology 55+/-15 vs 89+/-6.1% (P=0.05) and for those operated before 1990 vs after 1990 it was 63+/-8.1 vs 86+/-8.2% (P=0.04). CONCLUSIONS Mechanical MVR, in the current era, carries a low operative risk across the spectrum of paediatric age. Late survival is better for older children and those having no-AVSD pathology but it has improved substantially during the 1990s irrespective of age and disease aetiology.

Repair of tetralogy of Fallot in infancy with a transventricular or a transatrial approach

OBJECTIVE The optimal time and approach of repair of tetralogy of Fallot (TOF) remain controversial. The purpose of this study was to evaluate the outcome following repair of TOF in infants with particular regard to the surgical approach used. PATIENTS One hundred and sixty infants (mean age 195+/-89 days, range 11-364 days) undergoing repair of a simple TOF were studied. Between 1974 and 2000, a transventricular approach (RV) was used in 91 and between 1988 and 2000, a transatrial (RA) approach in 69 infants. Ten of these infants (6.2%) had a previous palliative shunt (four in the RV versus six in the RA group). A transannular patch (TAP) was inserted in 96 (60%) infants (76 versus 20). Follow-up was complete (mean 14.5+/-5.2 versus 6+/-1 years). RESULTS There were three operative deaths (1.9%), (two in RV versus one in RA group). A re-operation for right ventricular outflow tract obstruction (RVOTO) was performed in 19 patients (3 versus 16). Ten-year freedom from re-operation for RVOTO (+/-standard error of the mean) was 88+/-4% (98+/-2 versus 72+/-6%, P<0.0001). Within the RA group, 5-year freedom from re-operation for RVOTO for those who had a TAP was 79+/-9% and it was 75+/-4% for those having a simple repair. Six patients in the RV group required pulmonary valve replacement (PVR). Ten-year freedom from PVR was 98+/-1% (97+/-2 versus 100%, P=0.3). There were two late deaths, one in each group. Ten-year survival was 97+/-1%. One patient in the RV group developed late recurrent ventricular tachycardia requiring the implantation of a defibrillator. At most recent echocardiography, all but the patient who had the defibrillator had good right and left ventricular function. CONCLUSIONS Transventricular and transatrial repair of TOF in infancy, are associated with an acceptable operative risk, low incidence of late arrhythmia, good bi-ventricular function and excellent survival. In our experience, however, transatrial repair has a disturbing incidence of early and mid-term residual or recurrent RVOTO, even when a TAP has been used.

Open Commissurotomy for Critical Isolated Aortic Stenosis in Neonates

BACKGROUND The optimal management of critical aortic stenosis in early infancy remains controversial. The aim of this study was to assess the early and late outcomes following open surgical valvotomy for critical aortic stenosis in neonates and to provide a framework of data against which current results of other treatment approaches can be evaluated. METHODS Eighteen consecutive neonates (mean age 9.2 days, range 1 to 26 days) undergoing an open valvotomy for critical isolated aortic stenosis (the standard treatment for this condition in our unit) between 1984 and 2000 were studied. The mean aortic valve gradient was 79.4 mm Hg. Twelve neonates received prostaglandins and 10 received inotropic agents preoperatively. Follow-up was complete (mean 8.1 years, range 1 month to 15 years). RESULTS There was no operative mortality. At discharge, the mean aortic valve gradient was 37.2 mm Hg, with 6 patients having mild and 2 having moderate aortic regurgitation. Six patients required a reoperation; 3 of these had an aortic valve replacement at 9 to 11 years of age. Kaplan-Meier 5- and 10-year freedoms from any aortic reoperation or reintervention were 85 and 55%, respectively; 5- and 10-year freedoms from aortic valve replacement were 100 and 79%, respectively. A 14-year-old boy died from endocarditis 4 years following an aortic valve replacement in another unit. Kaplan-Meier 10-year survival was 100%. All survivors are in New York Heart Association I class and are leading normal lives. Their mean aortic valve gradient is 34.5 mm Hg, and none has significant aortic regurgitation. CONCLUSIONS Open valvotomy for critical aortic stenosis in neonates carries a low operative risk and provides lengthy freedom from recurrent stenosis or regurgitation. Reoperations are inevitable, but aortic valve replacement can be delayed until the implantation of an adult-sized prosthesis is possible. Late survival is excellent. We consider open surgical valvotomy to be the treatment of choice for critical neonatal aortic stenosis.

Arterialised hepatic nodules in the Fontan circulation: hepatico-cardiac interactions.

Hypervascular nodules occur commonly when there is hepatic venous outlet obstruction. Their nature and determinants in the Fontan circulation is poorly understood. We reviewed the records of 27 consecutive Fontan patients who had computerized tomography scan (CT) over a 4 year period for arterialised nodules and alterations in hepatic flow patterns during contrast enhanced CT scans and related these findings to cardiac characteristics. Mean patient age was 24 ± 5.8 years, (range 16.7-39.8) and mean Fontan duration was 16.8 ± 4.8 years (range 7.3-28.7). Twenty-two patients demonstrated a reticular pattern of enhancement, 4 a zonal pattern and only 1 demonstrated normal enhancement pattern. Seven (26%) patients had a median of 4 (range 1-22) arterialised nodules, mean size 1.8 cm (range 0.5 to 3.2 cm). All nodules were located in the liver periphery, their outer aspect lying within 2 cm of the liver margin. Patients with nodules had higher mean RA pressures (18 mmHg ± 5.6 vs. 13 mmHg ± 4, p=0.025), whereas their mixed venous saturation and aortic saturation was not significantly different (70% ± 11 vs. 67% ± 9 and 92% ± 10 vs. 94% ± 4, p>0.05). Post-mortem histology suggests focal nodular hyperplasia is the underlying pathology. ConclusionsAbnormalities of hepatic blood flow and the presence of arterialised nodules are common in the failing Fontan circulation. They occur especially when central venous pressures are high, and very likely indicate arterialisation of hepatic blood flow and reciprocal portal venous deprivation. The underlying pathology is most likely focal nodular hyperplasia.