Adri H. Cromme-Dijkhuis

Aortic root replacement with pulmonary autograft in children

Between September 1988 and February 1993, 14 patients whose ages ranged from 3 months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic root with the autologous pulmonary root for aortic valve disease. The follow-up was 4 years (cumulative total of 25.2 patient-years). There was no early mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to 21%). This patient had juvenile rheumatoid arthritis and died of consequent congestive heart failure with autograft failure 6 months after operation. Event-free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One patient was reoperated on because of autograft failure caused by a relapse of rheumatic fever. One patient operated on for critical neonatal aortic stenosis has subnormal exercise tolerance because of restrictive cardiomyopathy and pulmonary homograft regurgitation. The other 12 patients were in New York Heart Association functional class I at the end of follow-up. There was no prevalence of bacterial endocarditis. There were no signs of primary structural degeneration of the pulmonary autograft. During follow-up, in eight patients, increased anulus diameter of the pulmonary autograft could be demonstrated by precordial two-dimensional echocardiography, suggesting growth of the autograft. Our experience shows that aortic root replacement with the pulmonary autograft can be done with low mortality and morbidity in children with aortic valve disease. The operation seems to be contraindicated in children with juvenile rheumatoid arthritis because of the risk of recurrence of rheumatic disease in the autograft. The pulmonary autograft has also been shown to be susceptible to recurrence of rheumatic inflammation in children with a history of acute rheumatic fever. Despite pulmonary autograft replacement of the aortic valve in infants with critical valvular aortic stenosis and endocardial fibroelastosis, clinical results may be poor. Growth of the autograft is suggested by echocardiographic follow-up. We consider aortic root replacement with the pulmonary autograft the procedure of choice in children who require aortic valve replacement.

Right ventricular outflow tract reconstruction with an allograft conduit

BACKGROUND Allograft conduits are used for reconstruction of the right ventricular outflow tract in patients with congenital heart disease and in the pulmonary autograft procedure. A retrospective evaluation of our experience with the use of allograft conduits for reconstruction of the right ventricular outflow tract was conducted. METHODS Between August 1986 and March 1999, 316 allografts (246 pulmonary, 70 aortic) were implanted in 297 patients for reconstruction of the right ventricular outflow tract. Main diagnostic groups were aortic valve pathology (n = 112, 35%), tetralogy of Fallot (n = 71, 22%), and pulmonary atresia with ventricular septal defect (n = 46, 14%). Kaplan-Meier analyses were done for survival, valve-related reoperation, and valve-related events. In addition, Cox regression analysis was used for evaluation of potential risk factors. RESULTS Mean age at operation was 18 years (range, 7 days to 61 years). Mean follow-up was 4 years (range, 2 days to 12 years). Twelve patients (4%) died within 30 days after operation. Patient survival was 90% (95% confidence interval [CI], 86% to 94%) at 5 years and 88% (95% CI, 83% to 94%) at 8 years. Twenty-four reoperations were required for allograft dysfunction in 23 patients; 21 allografts were replaced. Freedom from valve-related reoperation was 91% (95% CI, 86% to 95) at 5 years and 87% (95% CI, 81% to 93%) at 8 years. Twenty-nine valve-related events were reported (2 deaths, 24 reoperations, 2 balloon dilatations, and 1 endocarditis). Freedom from valve-related events was 90% (95% CI, 85% to 94%) at 5 years after implantation, and 84% (95% CI, 77% to 91%) at 8 years. Risk factors for accelerated allograft failure were extra-anatomic position of the allograft (p = 0.03; hazard ratio, 9.7) and the use of an aortic allograft (p = 0.02; hazard ratio, 2.4). CONCLUSIONS Right ventricular outflow tract reconstruction with an allograft conduit has good medium-term results, although progression of allograft degeneration is noted. Aortic allografts should preferably not be used for reconstruction of the right ventricular outflow tract.

A broad and strong humoral immune response to donor HLA after implantation of cryopreserved human heart valve allografts

Cryopreserved human heart valves are used for valve replacement in patients with congenital or acquired heart disease. Although no blood group or human leukocyte antigens (HLA) matching is performed and no immunosuppression is administered, the clinical results are relatively good. After valve replacement, the majority of the patients develop HLA antibodies, whereas a smaller group of patients shows valve-related events at the long term after right ventricular outflow tract reconstruction. Therefore, we hypothesized that not the mere presence, but rather the titers of antidonor HLA antibodies may be related to valve allograft failure. The presence and specificity of HLA class I antibodies were determined by complement-dependent microlymphocytotoxicity (CDC) test in longitudinally taken peripheral blood samples of 35 valve allograft recipients. In eight patients with an antibody response specific against donor-HLA class I, the titers were measured by this CDC method after stepwise dilution of the plasma. Panel reactive antibodies of more than 10% were found in 31 of 35 (89%) valve allograft recipients. From these 31 patients, 24 (77%) developed donor-specific HLA class I antibodies. All eight selected patients had detectable donor-specific antibody titers, ranging from 1:2 to 1:8,000. Two donor valve recipients before retransplantation had (donor-specific) HLA antibodies and showed high titers of 1:256 and 1:8,000 shortly after the second allograft valve replacement, which was associated with an early graft failure in the latter patient. We conclude that transplantation of cryopreserved human heart valve allografts leads to a broad and strong humoral response, which is probably the result of a lack of immunosuppressive therapy after valve transplantation. Patients receiving a second or following valve allograft appeared to be sensitized and developed early and high allo-antibody titers after second valve allograft implantation. Valve failure was diagnosed in a patient with extremely high titers. These findings suggest that preoperative cross-matching may identify patients with high donor-specific HLA antibody titers and may reduce the risk for early recurrent graft failure.

Allograft reconstruction of the right ventricular outflow tract.

OBJECTIVE Evaluation of allograft reconstruction of the right ventricular outflow tract (RVOT). METHODS From 1986 to April 1995, 201 allografts (146 pulmonary, 55 aortic) were implanted in 189 patients for conduit reconstruction of the RVOT in congenital heart disease or in the pulmonary autograft procedure. The mean age at allograft implantation was 16 years (range 2 weeks - 54 years). The primary diagnoses of these patients were truncus arterious (n = 19, 10%), transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary atresia (PA) or stenosis (PS) (n = 14, 7%), PA with VSD (n = 26, 14%), PA or PS with intact septum (n = 7, 4%), tetralogy of Fallot (n = 44, 23%), corrected TGA with PA or PS (n = 11, 6%), tricuspid atresia (n = 9, 5%), aortic valve pathology for pulmonary autograft procedure (n = 55, 29%), and miscellaneous (n = 4, 2%). The allograft implantation was a reoperation in 54 patients (29%). RESULTS The mean follow-up was 2.5 years (range 4 weeks-9 years). Six patients died in hospital (3.2%). Patient survival at 5 years was 91% (95% CL 86-95%). Freedom from all valve-related events (2 deaths, 17 reoperations, one endocarditis), as determined during reoperation or autopsy at 5 years was 78% (95% CL 65-86%). Freedom from structural allograft failure was 83% (2 deaths, 12 reoperations, 95% CL 70-90%). Allografts implanted for congenital right heart defects failed earlier than allografts used for pulmonary autograft procedures (P = 0.05). Aortic allografts showed structural failure more often than pulmonary allografts (P = 0.05). There were more valve-related events in patients of a younger age at implantation (P = 0.02) and in those allograft valves from younger donors (P = 0.004). CONCLUSIONS Allograft RVOT reconstruction is an adequate surgical therapy. The allograft should preferably be pulmonary. A younger age at implantation is a risk factor for allograft failure. Donor age may be a thus-far underestimated risk factor for allograft degeneration.

The asymptomatic child a long time after the mustard operation for transposition of the great arteries

We studied 36 asymptomatic children 7.7 +/- 2.5 years after a Mustard operation. Fifteen children had sinus rhythm on all electrocardiograms made during follow-up. Only 2 had normal 24-hour Holter recordings throughout follow-up, 6 had periods of supraventricular tachycardia, and 3 had periods of atrial flutter. The electrophysiological evaluation of sinus node function was normal in 5 of the 31 children who were studied. The behavior of the atrial myocardium was electrophysiologically abnormal in most of the children. Atrioventricular node function, on the contrary, was normal in nearly all of the children. Eleven children had normal hemodynamics. Four had severe or complete obstruction of the superior vena cava, 1 had a severe pulmonary venous obstruction, 3 had a severe left ventricular outflow tract obstruction, and 2 had a large left-to-right shunt. Only 3 children had normal hemodynamic and electrophysiological studies. We conclude that the absence of symptoms and a normal routine examination of children a long time after a Mustard operation does not exclude hemodynamic and electrophysiological abnormalities, which can sometimes be severe. In view of these disappointing results, we decided to replace the Mustard operation with the arterial switch operation in children with transposition of the great arteries.

Clinical Outcome and Left Ventricular Function After Pulmonary Autograft Implantation in Children

BACKGROUND Aortic root replacement with a pulmonary autograft is an alternative treatment for children with aortic valve or root disease, or both. METHODS Twenty-six patients (18 boys and 8 girls) with a mean age of 10.9 years (range, 0.3 to 16.9 years) underwent this procedures in a 7-year period. The mean follow-up period was 3.2 years (range, 0.2 to 7.5 years). RESULTS During follow-up 3 patients died and one autograft was replaced with a mechanical valve. The actuarial survival and actuarial event-free survival rates were 87% and 79%, respectively, at both 5 and 7 years. None of the surviving patients had complaints, and all have done well and are living normal lives. Electrocardiographic signs of myocardial ischemia and left ventricular hypertrophy were not present. Echocardiography showed autograft valve regurgitation to be absent or trivial (n = 17) or mild (n = 5). Stenosis was not present. Increasing autograft annulus diameters were noted during follow-up, but this was not related to the severity of autograft regurgitation. Left ventricular dimensions and function were within normal limits later than 1 year after the operation. Only 2 patients had a moderate pulmonary stenosis without right ventricular hypertrophy. CONCLUSIONS The surgical results, clinical outcome, valve function, and left ventricular function in our patients have been good. This procedure is recommended as a method of aortic valve replacement in children.

Repair of aortic arch interruption by direct anastomosis.

OBJECTIVE Evaluation of surgical treatment of interrupted aortic arch (IAA) by direct anastomosis. METHODS A consecutive series of 17 infants with IAA (type A in eight patients, type B in nine) were operated upon. The mean age at arch repair was 1.0 month (range 0.2-7.7), mean weight was 3.7 kg (range 2.2-6.2). All arch repairs were done by direct anastomosis. This included a persistent arterial duct in one and a subclavian turnup in another case. The aortic reconstruction included reimplantation of a lusoric artery in three patients, patch enlargement of the ascending aorta in three and of the complete arch in one patient. The arch repair was done through a lateral thoracotomy in three patients. In 14 patients the aortic repair was part of a single-stage approach through a median sternotomy using cardiopulmonary bypass and circulatory arrest. RESULTS There was no operative mortality. One patient (single-stage approach) died 2 days after operation due to respiratory problems caused by tracheobronchomalacy. One patient (lateral approach) died suddenly 3 months after aortic repair and banding. Median follow up was 4.8 years (range 0.1-12.9). In five patients restenosis of the aortic arch developed, all within 1.5 years after repair. This was not correlated with the type of interruption, weight at operation, age at operation or the surgical approach. The actuarial freedom from restenosis was 61% at 5 years with a 70% confidence limit (CL70%) of 46-75. All restenoses were balloon dilated, but two needed redo surgery, which was done by the median approach. In three patients discrete subaortic stenosis developed. This was not correlated with the type of interruption, weight at operation, age at operation or the surgical approach. The actuarial freedom from subaortic stenosis was 68% at 5 years (CL70% = 54-83). These stenoses were treated by enucleation, followed in one patient by a pulmonary autograft procedure for recurrent root stenosis after another year. At the end of follow up all patients were thriving well, lacked symptoms, were normotensive and had normal femoral artery pulsations. CONCLUSIONS IAA can be treated well with primary anastomosis. Possible restenosis of the aortic arch can adequately be treated by percutaneous balloon dilatation or redo surgery if necessary. Arch repair by median single-stage approach has our preference.

A randomized, placebo-controlled GH trial in very preterm infants who were at risk for bronchopulmonary dysplasia and were treated with dexamethasone

Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg · kg−1 · d−1, tapering off every third day). Simultaneously, high-dose GH (0.3 mg · kg−1 · d−1) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5–0.3 mg · kg−1 · d−1), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, high-dose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA.