[Apoptotic deregulation of endothelial cells and intimal proliferation in pulmonary hypertension of congenital heart disease]. / Dysrégulation apoptotique des cellules endothéliales et prolifération intimale dans l'hypertension artérielle pulmonaire des cardiopathies congénitales.

OBJECTIVES: To assess the cellular and histological basis of irreversible pulmonary hypertension (PHT) in the clinical setting of congenital heart disease (CHD). BACKGROUND: Although many children with CHD develop pulmonary vascular disease, it is unclear why this complication is reversible after complete repair in some cases but irreversible in others. As failure of endothelial cell apoptosis might lead to intimal proliferation and lack of reversibility of PHT, we investigated this and other key markers of vasoactivity and angiogenesis, in subjects with PHT and CHD. METHODS: We assessed anti- and pro-apoptotic markers in vascular and perivascular cells in lung biopsies from 18 patients with CHD; 7 with reversible and 11 with irreversible PHT, and from 6 controls. Immunostaining for eNOS, VEGF and CD34 (markers of vasoactivity and neoangiogenesis) was also performed. RESULTS: The anti-apoptotic protein Bcl-2 was highly expressed by pulmonary endothelial cells in all cases of irreversible PHT but in no cases of reversible PHT, nor in controls (p<0.001). Intimal proliferation was present in 10/11 irreversible PHT cases but never observed in reversible PHT (p<0.001). Similarly, perivascular inflammatory T-cells expressed more anti-apoptotic proteins in irreversible PHT (p<0.01). Irreversible PHT cases were also more likely to show compensatory up-regulation of VEGF and new small vessel formation at the sites of native vessel stenosis or occlusion (p<0.001). CONCLUSION: Irreversible PHT is strongly associated with impaired endothelial cell apoptosis and anti-apoptotic signalling from perivascular inflammatory cells. These changes are associated with intimal proliferation and vessel narrowing and thereby may contribute to clinical outcomes associated with pulmonary hypertension. Markers of apoptosis and angiogenesis were assessed in lung biopsies of subjects with pulmonary hypertension (PHT) due to congenital heart disease (CHD). The anti-apoptotic protein Bcl-2 was strongly expressed by pulmonary endothelial cells in irreversible PHT (n=11) but never in reversible PHT (n=7) (p<0.01). Irreversible PHT was also associated with up-regulation of VEGF and new vessel formation around occluded native vessels (p<0.01).

[Endothelial vasoactive factors: predictive markers of the results of the Fontan intervention?]. / Facteurs vasoactifs endothéliaux: marqueurs prédictifs du résultat de l'intervention de Fontan?

UNLABELLED: We retrospectively analyzed the pulmonary biopsies of a Fontan intervention in order to identify predictive markers of its result. The pulmonary biopsies of 17 patients who benefited from the Fontan intervention and 6 controls were studied. The histomorphometric measurements and endothelial expression of vasoactive factors (NO synthase, endothelin-1) and angiogenic factors (VEGF) were analyzed with immunohistochemistry at the level of intra-acini pulmonary arterioles. Eight patients presented a good surgical result (group 1). Distal arterioles presented a thin and regular wall: the NO synthase, endothelin and VEGF expression was low. Nine patients presented a failure of the Fontan operation (group 2). The distal arterioles were slightly musculated (p<0.01 vs. group 1 and group control). The endothelin-1 expression was comparable to that observed in group 1. Conversely, the NO synthase and VEGF expressions were significantly increased in that group (<0.001 vs. group 1 and group control). CONCLUSION: In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. This study could be able to define predictive factors of the evolution and refine the selection of patients candidate for a Fontan operation.

Fontan completion: intracardiac tunnel or extracardiac conduit?

The concept of Fontan circulation was first clinically introduced in 1971. Since that time, many technical modifications have been advocated. Among them, the concept of total cavopulmonary connection, introduced in the late 80's, has experienced widespread use over the past 10 years. In this procedure, a bidirectional superior cavopulmonary anastomosis is performed while the inferior caval blood flow is directed towards the pulmonary arteries through an intraatrial composite tunnel. More recently, an extracardiac conduit to divert inferior vena cava flow to the pulmonary arteries has been advocated. The respective merits of these two approaches remain to be determined.

Absorbable pulmonary artery banding in tricuspid atresia.

A child with tricuspid atresia, concordant ventriculoarterial connections, large ventricular septal defect, and elevated pulmonary artery pressure underwent pulmonary artery banding with a polydioxanone ribbon. This procedure was successful in this patient as the ventricular septal defect became restrictive while the banding was fully absorbed after 5 months. This technique could be included in the panel of surgical strategies for patients with single ventricle physiology and potential but insufficient subpulmonary stenosis in early infancy.

Bi-directional cavopulmonary shunt: is accessory pulsatile flow, good or bad?

OBJECTIVE: Evaluation of the effect and long-term outcome of accessory pulsatile blood flow versus classical bi-directional cavopulmonary connection (BCPC). METHODS: Retrospective review of the medical and surgical records. RESULTS: Two-hundred and five patients (119 boys, 86 girls) underwent BCPC from 1990 to 1996. Accessory pulsatile flow was present in 68%, flow being maintained through the pulmonary trunc in 46%, systemic-to-pulmonary artery shunt in 13% and mixed in 7%, or patent ductus arteriosus in 2%. Patients with accessory pulsatile flow had lower hospital mortality (3% versus 5%), while mean pulmonary artery pressure (14.1 versus 12.6 mmHg P = 0.050) and increase of oxygen saturation (12.4 versus 8.7, P = 0.034) were significantly higher. The period of artificial ventilation (1.9 day) and ICU stay (6 days) did not differ for both groups. Late mortality was higher following accessory pulsatile flow (6% versus 1%). At late follow-up patients with accessory pulsatile flow had significantly higher oxygen saturation (mean 85 +/- 4%, versus 79 +/- 4%; P < or = 0.005). If subsequent completion of Fontan is considered the optimal palliation and subsequent systemic to pulmonary artery shunt, arteriovenous fistula and transplantation is considered a failure, patients with accessory pulsatile flow had significantly more and earlier completion of the Fontan procedure (mean 1.7 +/- 2.4 years, versus 2.7 +/- 4.4 years; P = 0.008). Survival is not influenced by age at bi-directional cavopulmonary shunt surgery, left or right functional ventricular anatomy or previous palliative surgery. One patient with accessory pulsatile flow developed systemic-to-pulmonary collateral's eventually requiring lobectomy. CONCLUSION: Despite two different initial palliative techniques the outcome was not significantly different. Accessory pulsatile blood flow appeared not to be a contra-indication for a completion Fontan procedure. Moreover, the data suggest that after accessory pulsatile flow can safely be performed, at late follow-up oxygen saturation is higher, while, significantly more and earlier completion of Fontan occurred. Age at bi-directional cavopulmonary shunt, basic left or right ventricular anatomy or previous palliative surgery did not influence survival.

Surgical angioplasty of the main coronary arteries in children.

OBJECTIVE: To determine the safety and efficacy of surgical angioplasty of the coronary arteries in children. METHODS: We performed 9 surgical reconstructions of the left main coronary artery and 1 of the right coronary artery ostium in 10 children (mean age 5.7 years; range 2 months-15 years). The basic diseases included the following: congenital atresia of the left coronary artery (n = 2) and atresia of the right coronary artery in a patient with an aortoventricular tunnel (n = 1); stenosis of the left main coronary artery (1) in a patient with Williams syndrome (n = 1), (2) in a patient with familial hypercholesterolemia (n = 1), (3) after the arterial switch operation for transposition of the great arteries (n = 3), (4) after reimplantation of an anomalous left main coronary artery from the pulmonary artery (n = 1), and (5) by compression after a réparation à l'étage ventriculaire procedure (n = 1). Myocardial viability was assessed by single photon emission computed tomography (thallium 201; 7/10). The coronary artery stem was enlarged with a saphenous (n = 5), a pericardial (n = 4), or a polytetrafluoroethylene patch (n = 1). RESULTS: There was 1 hospital death and 9 patients are alive (mean follow-up 46 +/- 30 months; range 12 months to 10.5 years). Eight of 9 survivors had a selective coronary artery angiogram and had normal coronary artery ostia. Two patients had stenosis of the left anterior descending coronary artery, 1 of whom underwent successful internal thoracic artery grafting. CONCLUSIONS: Surgical angioplasty of the coronary stems restores physiologic coronary perfusion and conserves bypass material. It can be performed safely in children and provides encouraging midterm results.

Neonatal arterial switch operation: coronary artery patterns and coronary events.

OBJECTIVE: To determine the incidence of coronary events following neonatal arterial switch and to identify potential risk factors for death and coronary events. METHODS: The total experience (236 consecutive arterial switch operations) of one surgeon was studied. Associated procedures included ventricular septal defect closure in 37 patients (16%) and aortic arch repair in 14 patients (6%)). The influence of various patient, procedural, support technique and experience variables was analyzed. RESULTS: There were 19 deaths (8-70% confidence limits = 6-10%). Survival at 1 month, 1 year and 5 years was 93, 92 and 92%, respectively. Risk factors for death included small birth weight (P = 0.0015), hypoplasia of right ventricle (P < 0.0001), aortic arch obstruction (P < 0.0001) and coronary patterns with coronary arteries coursing between the great arteries (P = 0.0066). Coronary events occurred in 26 patients (11-70% confidence limits = 9-13%) and involved coronary deaths (11 patients), non fatal myocardial infarctions (8 patients) and coronary stenoses or occlusions (7 patients). Freedom from coronary events at 1 month, 1 year and 5 years was 94, 91 and 88%, respectively. Risk factors for coronary events included coronary patterns with retropulmonary course of the left main or left circumflex coronary artery (P = 0.0122), coronary patterns with coronary arteries coursing between the great arteries (P < 0.0001), all variations of intramural coronary arteries (P = 0.0010) and commissural origin of coronary ostia (P = 0.0171). CONCLUSIONS: (1) In most neonates, arterial switch operation carries a low operative risk and provides excellent mid-term results; (2) The operative risk remains increased in some subsets; and (3) Some coronary patterns increase the risk of coronary events. Further surgical experience may improve the results.

"Classic" repair of congenitally corrected transposition and ventricular septal defect.

BACKGROUND: This study examined the results of "classic" repair of congenitally corrected transposition of the great arteries and ventricular septal defect. METHODS: From 1974 to 1994, 52 patients underwent a classic complete repair of lesions associated with congenitally corrected transposition. They were divided into two groups: ventricular septal defect plus left ventricular outflow tract obstruction (group I, 37 patients) and isolated ventricular septal defect (group II, 15 patients). Tricuspid plasty or replacement was performed primarily in 1 patient of group I (3%) and in 8 patients of group II (53%). RESULTS: The overall operative mortality was 15% (8/52 patients), and the incidence of postoperative atrioventricular block was 27% (14/52 patients). Eight patients died secondarily, 5 of heart failure. Survival rates were 83% +/- 6% at 1 year and 55% +/- 14% at 10 years for group I and 86% +/- 9% at 1 year and 71% +/- 12% at 10 years for group II (not significant). Redo tricuspid plasty or replacement was performed in 12 patients. CONCLUSIONS: Results of classic complete repair of lesions associated with congenitally corrected transposition are not satisfactory in our experience because (1) the operative mortality and the incidences of tricuspid valve replacement and atrioventricular block are high and (2) secondary heart failure is frequent. However, a retrospective review of morphologic findings shows that "anatomic" complete repairs would not have been feasible in 6 of our patients.

Arterial switch operation: a new technique of coronary transfer.

A successful outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) depends in large part on the adequacy of transfer of the coronary arteries to the neoaorta. The present paper describes a new technique of coronary transfer which was used in 43 patients: 28 neonates with TGA and intact septum (with coarctation in one), 10 neonates with TGA and ventricular septal defect (with coarctation in one), 2 children undergoing ASO after failed Senning operation and 3 patients with complex TGA. A standardized uniform technique of coronary transfer was used; this technique involved reimplantation of the two coronary ostia side by side after excision of a single button of neoaortic wall. Most coronary patterns were encountered: the usual pattern in 30, circumflex from right coronary artery in 7, inverted coronary arteries in 3, inverted circumflex and right coronary arteries in 3. There was no early coronary-related mortality or morbidity. One late death (3 months) was probably coronary-related. The overall coronary risk was 2.3% (70% confidence limits = 0.3%-7.5%). The proposed technique of coronary transfer can be used in most patients with TGA (all patients without coronary arteries running between the great arteries) and entails a low coronary risk.

Surgical treatment of multiple ventricular septal defects using a biologic glue.

The closure of multiple ventricular septal defects remains a surgical challenge. Mortality and morbidity are high. Left ventricular incision and multiple patches or stitches impair septal motion and function. We searched for a method that would cause minimal left ventricular and septal dysfunction. The use of fibrin seal for closing ventricular septal defects was considered. The method was first tested in animals so as to assess the internal resistance of the fibrin seal to stretching and fragmentation in addition to its adhesiveness and hence the absence of left-to-right embolization of the fibrin seal clot and the long-term success of the ventricular septal defect closure further to complete resorption of the ventricular septal defect clot. This experimental work was very satisfactory. Between April 1986 and September 1991, 15 children were operated on with the use of this technique. The overall hospital mortality rate was 6%. There were no reoperations for residual ventricular septal defects. All the long-term survivors (n = 13) were in excellent clinical condition with no or trivial residual shunt attested by color flow mapping investigation. This experimental and clinical experience suggests that satisfactory results can be achieved with the use of fibrin seal for the closure of multiple muscular ventricular septal defects.

Pediatric cardiac transplantation for congenital heart defects: surgical considerations and results.

Among 54 children who underwent 55 heart transplantations, 24 (44%) (mean age, 4.9 +/- 4.8 years; range, 9 days to 18 years) had congenital defects with the following diagnoses: single-ventricle variants (6), hypoplastic left heart syndrome variants (5), transposition complex (6), and miscellaneous defects (7). Twenty patients (83%) had undergone 43 prior operations. Additional surgical procedures included repositioning of transposed great arteries (11), reconstruction of the aortic pathway (4), reconstruction of the pulmonary pathway (8), correction of situs inversus (1), and correction of anomalous pulmonary (1) or systemic (1) venous drainage. Reconstructive procedures were performed using donor or recipient tissue or both. There were six early deaths (hyperacute rejection, 1 patient; pulmonary hypertension, 1; graft failure, 2 patients; infection, 2) and six late deaths (sudden death, 2; chronic rejection, 2; nonspecific graft dysfunction, 1; lymphoproliferative disease, 1). The survival rate was 43% +/- 12% at 3 years. No deaths were related to surgical technique. Survival was not significantly different in pediatric recipients with cardiomyopathy (67% +/- 9%; p = 0.22). Accelerated coronary artery disease was noted in 4 operative survivors (22%; 70% confidence limits, 12% to 36%). All late survivors were free from cardiac symptoms after a mean follow-up of 34 +/- 24 months (range, 6 to 71 months). Based on this study, we reached three conclusions. (1) Careful planning of both harvesting and transplantation procedures allows heart transplantation in recipients with congenital heart diseases. (2) The surgical technique may be demanding, but the early risk is not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse subaortic stenosis: modified Konno procedures with aortic valve preservation.

The Konno procedure provides adequate relief of diffuse subaortic stenosis but requires aortic valve replacement. This may be questionable in patients without aortic valve lesions. Eleven patients had diffuse subaortic stenosis and normal aortic orifice: tunnel subaortic stenosis (6 patients) or diffuse hypertrophic obstructive cardiomyopathy (5 patients). The mean age was 16 +/- 14 years (range: 3 months to 45 years). The mean subaortic gradient was 95 +/- 24 mmHg (range: 60 to 150 mmHg). Two patients had previously undergone resection of discrete subaortic stenosis. Modified Konno procedures were used: aortoseptal approach with aortic annulus division in 5 patients, conal enlargement without aortic annulus division in 6 patients. There was one early death (9%, 70% CL = 1%-27%) and no late deaths. Reoperation was required in two patients: one early for iatrogenic aortic regurgitation and one late for residual ventricular septal defect and mitral regurgitation. The mean follow-up was 3.8 +/- 4.2 years (range: 2 months to 10 years). The survivors were in functional class I (8/10), had a normal left ventricular function (9/10), were in sinus rhythm (10/10) and had left ventricular outflow tract gradients ranging up to 25 mmHg (mean = 6 +/- 10 mmHg). Residual surgery-related defects included ventricular septal defect (one) and aortic regurgitation (one). In patients with diffuse subaortic stenosis and normal aortic orifice, modified Konno procedures with aortic valve preservation are preferable, effective and can be safely performed in infants and children.

Anomalous left coronary artery from the pulmonary artery: results of isolated aortic reimplantation.

Thirty-one consecutive children with anomalous left coronary artery underwent direct aortic reimplantation of the anomalous artery without an associated procedure. There were five deaths (16%; 70% confidence limits, 9% to 26%), three in the hospital and two early (within 3 months). The severity of preoperative left ventricular dysfunction was the only incremental risk factor for mortality: 31% mortality rate among patients with left ventricular shortening fraction of less than 0.20 versus 0% among patients with a left ventricular shortening fraction of 0.20 or more (p = 0.03). There were no late deaths up to 6 years, a survival rate of 84% +/- 7%. Late results were studied in 23 survivors having a follow-up of longer than 12 months. Ninety-six percent were free of symptoms; left ventricular function recovered to normal in all patients; moderate to severe mitral regurgitation decreased to minimal or no regurgitation in most patients (5/7); and the reimplanted anomalous left coronary artery was patent in each patient. Based on this study, we reached five conclusions. (1) Direct aortic reimplantation is technically feasible in most patients with anomalous left coronary artery and yields a high rate of late patency. (2) Left ventricular resection is unnecessary. (3) The mitral valve should not be interfered with at the initial operation, but mitral regurgitation may persist in a few patients and necessitate later operation. (4) In patients with moderate left ventricular dysfunction, the operative risk is low and early operation indicated. (5) In patients with severe left ventricular dysfunction, the operative risk is high; heart transplantation may be suggested, but our current approach favors an immediate corrective procedure.

Transposition of the great arteries, ventricular septal defect, and pulmonary outflow tract obstruction. Rastelli or Lecompte procedure?

During a 10-year period (1980 to 1990), 62 patients underwent complete repair for transposition of the great arteries, ventricular septal defect, and pulmonary outflow tract obstruction. Twenty-two patients (35%) (mean age 8.1 +/- 7.2 years) underwent the Rastelli operation: The ventricular septal defect was enlarged anteriorly in eight patients, and right ventricular-pulmonary artery continuity was established with an extracardiac valved (9/22) or nonvalved (13/22) conduit. Forty patients (65%) (mean age 3.3 +/- 3.2 years) underwent the Lecompte modifications: The conal septum was extensively excised when present (30/40), anterior translocation of the pulmonary bifurcation was performed in 32 patients, and right ventricular-pulmonary artery continuity was established by direct anastomosis without a prosthetic conduit. There were seven early deaths (11%; 70% confidence limits, 7% to 17%): two after the Rastelli procedure (9%; 70% confidence limits, 3% to 20%) and five after the Lecompte operation (12.5%; 70% confidence limits, 7% to 20%). Four patients were lost to follow-up, yielding a 93% complete follow-up (mean follow-up 55 months). There were two late deaths (one in each group). Actuarial probability of survival (+/- standard error) at 5 years was 83% +/- 9% after the Rastelli operation and 84% +/- 6% after the Lecompte procedure. All long-term survivors (except one in the Rastelli group) were in functional class I. Five patients in the Rastelli group underwent late reoperation for obstruction of the extracardiac conduit (28%; 70% confidence limits, 16% to 42%). Three late reoperations (10%; 70% confidence limits, 4% to 19%) were required after the Lecompte operation (one for residual ventricular septal defect and two for residual pulmonary outflow tract obstruction). At most recent examination, residual pulmonary outflow tract obstruction was present in seven patients of the Rastelli group (39%; 70% confidence limits, 26% to 53%) and in six patients of the Lecompte group (19%; 70% confidence limits, 12% to 29%). The combined likelihood of reoperation for pulmonary outflow tract obstruction and residual pulmonary outflow tract obstruction was significantly higher in the Rastelli group (67% versus 26%; p = 0.005). Both procedures provide satisfactory early and late results. The Lecompte operation allows complete repair in infancy, is feasible in patients with anatomic contraindications to the Rastelli operation, and may reduce the need for reoperation and the prevalence of residual pulmonary outflow tract obstruction.