The first multicentre study on coronary anomalies in the Netherlands: MuSCAT.

BACKGROUND: Current guidelines on coronary anomalies are primarily based on expert consensus and a limited number of trials. A gold standard for diagnosis and a consensus on the treatment strategy in this patient group are lacking, especially for patients with an anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) with an interarterial course. AIM: To provide evidence-substantiated recommendations for diagnostic work-up, treatment and follow-up of patients with anomalous coronary arteries. METHODS: A clinical care pathway for patients with ACAOS was established by six Dutch centres. Prospectively included patients undergo work-up according to protocol using computed tomography (CT) angiography, ischaemia detection, echocardiography and coronary angiography with intracoronary measurements to assess anatomical and physiological characteristics of the ACAOS. Surgical and functional follow-up results are evaluated by CT angiography, ischaemia detection and a quality-of-life questionnaire. Patient inclusion for the first multicentre study on coronary anomalies in the Netherlands started in 2020 and will continue for at least 3 years with a minimum of 2 years of follow-up. For patients with a right or left coronary artery originating from the pulmonary artery and coronary arteriovenous fistulas a registry is maintained. RESULTS: Primary outcomes are: (cardiac) death, myocardial ischaemia attributable to the ACAOS, re-intervention after surgery and intervention after initially conservative treatment. The influence of work-up examinations on treatment choice is also evaluated. CONCLUSIONS: Structural evidence for the appropriate management of patients with coronary anomalies, especially (interarterial) ACAOS, is lacking. By means of a structured care pathway in a multicentre setting, we aim to provide an evidence-based strategy for the diagnostic evaluation and treatment of this patient group.

Dealing with kinked and swirled pulmonary vessels: surgical treatment of arterial tortuosity syndrome: a case report.

We present the case of a child with arterial tortuosity syndrome, describing the operative findings and our surgical technique to address pulmonary arteries stenosis.

Ventricular assist device implantation in patients with a failing systemic right ventricle: a call to expand current practice.

Ventricular assist device (VAD) implantation is an established treatment modality for patients with end-stage heart failure, and improves symptoms and survival. In the Netherlands, it is not yet routinely considered in patients with congenital heart disease and failing systemic right ventricle (SRV). Recently, a VAD was implanted in 2 SRV patients, one who underwent a Mustard procedure during infancy for transposition of the great arteries (male, 47 years old) and one with a congenitally corrected transposition of the great arteries (male, 54 years old). The first patient is doing well >1 year after implantation; the second patient will be discharged home soon. These examples and other reports demonstrate the feasibility of adopting VAD implantation into routine care for SRV failure. In conclusion, patients with SRV failure may be suitable candidates for VAD implantation: they are relatively young, usually have a preserved subpulmonary left ventricular function, and their specific anatomical and physiological characteristics often make them unsuitable for cardiac transplantation. Therefore it is important to recognise the possibility of VAD implantation early in the process of SRV failure, and to timely refer these patients to a heart failure clinic with experience in VAD implantation in this group of patients for optimisation, screening, and implantation.

Tailored circulatory intervention in adults with pulmonary hypertension due to congenital heart disease.

BACKGROUND: Adults with pulmonary hypertension associated with congenital heart disease (PH-CHD) often have residual shunts. Invasive interventions aim to optimise pulmonary flow and prevent right ventricular failure. However, eligibility for procedures strongly depends on the adaptation potential of the pulmonary vasculature and right ventricle to resultant circulatory changes. Current guidelines are not sufficiently applicable to individual patients, who exhibit great diversity and complexity in cardiac anomalies. METHODS AND RESULTS: We present four complex adult PH-CHD patients with impaired pulmonary flow, including detailed graphics of the cardiopulmonary circulation. All these patients had an ambiguous indication for shunt intervention. Our local multidisciplinary Grown-Ups with Congenital Heart Disease team reached consensus regarding a patient-tailored invasive treatment strategy, adjacent to relevant guidelines. Interventions improved pulmonary haemodynamics and short-term clinical functioning in all cases. CONCLUSIONS: Individual evaluation of disease characteristics is mandatory for tailored interventional treatment in PH-CHD patients, adjacent to relevant guidelines. Both strict registration of cases and multidisciplinary and multicentre collaboration are essential in the quest for optimal therapy in this patient population.

Platypnoea-orthodeoxia syndrome, an underdiagnosed cause of hypoxaemia: four cases and the possible underlying mechanisms.

Cardiac platypnoea-orthodeoxia syndrome (POS) is a position-dependent condition of dyspnoea and hypoxaemia due to right-to-left shunting. It often remains unrecognised in clinical practice, possibly because of its complex underlying pathophysiology. We present four consecutive patients with POS and patent foramen ovale (PFO) who underwent a successful percutaneous PFO closure, describe the mechanism of their POS and provide a review of the literature.

Surgery in adults with congenital heart disease.

BACKGROUND: A significant proportion of patients with congenital heart disease require surgery in adulthood. We aimed to give an overview of the prevalence, distribution, and outcome of cardiovascular surgery for congenital heart disease. We specifically questioned whether the effects of surgical treatment on subsequent long-term survival depend on sex. METHODS AND RESULTS: From the Dutch Congenital Corvitia (CONCOR) registry for adults with congenital heart disease, we identified 10 300 patients; their median age was 33.1 years. Logistic and Cox regression models were used to assess the association of surgery in adulthood with sex and with long-term survival. In total, 2015 patients (20%) underwent surgery for congenital heart disease in adulthood during a median follow-up period of 15.1 years; in 812 patients (40%), it was a reoperation. Overall, both first operations and reoperations in adulthood were performed significantly more often in men compared with women (adjusted odds ratio=1.4 [95% confidence interval, 1.2-1.6] and 1.2 [95% confidence interval, 1.0-1.4], respectively). Patients with their third and fourth or more surgery in adulthood had a 2- and 3-times-higher risk of death compared with patients never operated on (adjusted hazard ratio=1.9 [95% confidence interval, 1.0-3.6] and 2.7 [95% confidence interval, 1.1-6.3], respectively). Men with a reoperation in adulthood had a 2-times-higher risk of death than women (adjusted hazard ratio=1.9; 95% confidence interval, 1.0-3.5). CONCLUSIONS: Of predominantly young adults with congenital heart disease, one fifth required cardiovascular surgery during a 15-year period; in 40%, the surgery was a reoperation. Men with congenital heart disease have a higher chance of undergoing surgery in adulthood and have a consistently worse long-term survival after reoperations in adulthood compared with women.

Two cases of aorto-right atrial tunnel: clinical presentation, imaging and percutaneous closure.

Communication between the aortic sinus and a cardiac chamber is a rare anomaly that can be diagnosed in children and young adults. We describe two cases with a tunnel between the aortic sinus and right atrium, discuss diagnostic modalities, and review the literature on this anomaly.

[Percutaneous implantation of a pulmonary valve in 3 children with surgically corrected cardiac anomalies]. / Percutane implantatie van een pulmonalisklep bij 3 kinderen met chirurgisch gecorrigeerde hartafwijkingen.

An 11-year-old girl, a 15-year-old boy and a 12-year-old girl all underwent percutaneous implantation of a Melody pulmonary valve prosthesis to replace a stenotic and insufficient homograft in the pulmonary artery. Preoperatively, 2 of the children suffered from fatigue and dyspnoea on exertion The homografts had been implanted between the ages of 1-2, to establish surgical continuity between the right ventricle and the pulmonary artery. The anomalies were tetralogy of Fallot, pulmonary atresia with intact ventricular septum and pulmonary atresia with a ventricular septum defect. Percutaneous pulmonary valve replacement was successful in all 3 patients. After implantation, right ventricular pressure decreased to 30% of systemic pressure and regurgitation was not observed. All patients were discharged in a good condition on the day after the implantation. Percutaneous pulmonary valve replacement is a promising technique with good short-term results. In selected patients this percutaneous technique can substitute or postpone the surgical replacement ofa stenotic or insufficient homograft.

[Mechanical circulatory support after paediatric cardiac surgery]. / Mechanische ondersteuning van de circulatie na kinderhartchirurgie.

When circulatory failure occurs after paediatric cardiac surgery despite conventional therapy (inotropic medication, optimising pre- and afterload) mechanical assist devices can be used. Assist devices can be categorised in different ways: according to the type of pump used (centrifugal, axial flow, or pneumatic), according to univentricular or biventricular support and in relation to the presence of an oxygenator. Paediatric devices are non-implantable. Extra-corporeal membrane oxygenation (ECMO) consists of a roller pump and a membrane oxygenator and is a relatively simple means of biventricular cardiac support while respiratory support is provided at the same time. All other devices lack the oxygenator and thus provide only circulatory support. The main disadvantage of ECMO is that it can be used for a maximum of several weeks while modern pneumatic assist devices (MEDOS, Berlin Heart) can be used for several months. Thromboembolic events, bleeding and sepsis are the main complications of all assist devices. The use of circulatory assist devices can increase the chances of survival when severe cardio(pulmonary) failure occurs following surgical correction of congenital heart defects.

[Favourable results with surgical treatment in 43 children with hypoplastic left-heart syndrome or similar disorders, 1999-2005]. / Gunstige resultaten van chirurgische behandeling van 43 kinderen met het hypoplastisch linkerhartsyndroom of een equivalente afwijking, 1999/'05.

OBJECTIVE: To describe the results of surgical treatment of hypoplastic left-heart syndrome (HLHS) and HLHS-like disorders in the Amsterdam-Leiden Centre for Congenital Heart Disease, the Netherlands. DESIGN: Retrospective, descriptive. METHOD: Data were collected on 43 neonates with HLHS or similar disorders who underwent surgical treatment between December 1999 and December 2005. HLHS was present in 37 patients and 6 had disorders similar to HLHS (unbalanced atrioventricular septal defect, truncus arteriosus with hypoplastic left ventricle, double inlet left ventricle). Surgery was performed in 3 steps: Norwood operation shortly after birth (n = 43), bidirectional cavopulmonary anastomosis a few months later (n = 30) and total cavopulmonary connection at the age of 2-3 years (n = 10). During the Norwood operation, the first 21 patients received a modified Blalock shunt (between the right brachiocephalic artery and pulmonary artery), whereas the following 22 patients received a Sano shunt (between the right ventricle and pulmonary artery). RESULTS: Of the 43 patients, 11 died: 7 within 30 days of the first operation, 2 between the first and second operation, and 2 between the second and third operation. Actuarial survival for the entire group is 74% (32/43). The mortality rate was lower with the Sano shunt (9%; 2/22) than with the modified Blalock shunt (43%; 9/21). Catheter interventions were necessary in 10 patients: 6 had balloon dilatation of the distal aortic arch and 4 had balloon dilatation/stent placement for narrowed pulmonary arteries. With a median follow-up of 22 months (range: 1-75), 2 patients had marked neurological side effects. All 32 surviving patients were in good clinical condition.

[Complete atrioventricular septal defect in children with Down's syndrome: good results of surgical correction at younger and younger ages]. / Compleet atrioventriculair septumdefect bij kinderen met het syndroom van Down: goede resultaten van chirurgische correctie op steeds jongere leeftijd.

OBJECTIVE: To evaluate the results of cardiosurgical treatment of children with Down's syndrome and a complete atrioventricular septal defect (cAVSD). DESIGN: Retrospective. METHOD: Data were collected from the records of all patients with Down's syndrome who had been subjected to primary corrective surgery for cAVSD in the period 1980-2003 in Leiden, The Netherlands. Exclusion criteria were: concomitant tetralogy of Fallot or interruption of the aortic arch and palliative banding of the pulmonary artery. Children with an abnormal shape of the ventricle making it impossible to correct biventricularly were not considered in the study. Data on mortality >30 days after the operation and on repeated surgery were included in the analysis if the duration of follow-up was at least 5 years. RESULTS: The group comprised 148 children: 75 girls and 73 boys. The median age at time of surgery was 20 weeks (range: 6 weeks to 3.7 years) and showed a statistically significant decrease during the period under investigation. Of 4 children lost to clinical follow-up actual data could be obtained. The median duration offollow-up was 6 years and 7 months (range: 38 days to 23 years and 11 months). 28 children (19%) died. The mortality within 30 days after the operation decreased from 0-38% in the period 1980-1989 via 0-30% in the period 1990-1999 to 0% in 2000-2003. The percentage ofreoperations related to the correction ofcAVSD (14%; 14/98) did not seem to increase. Of the correction-related reoperations, 14% (2/14) were followed by a second reoperation. Conclusion. In the period 1980-2003, children with Down's syndrome and a cAVSD were corrected surgically at a younger and younger age. The early mortality decreased to 0% in the years 2000-2003. Echocardiography in the first weeks of life for all children with Down's syndrome makes it possible to diagnose those with a cAVSD early enough for surgical repair.

Postsurgical course of patients with congenitally corrected transposition of the great arteries.

Because congenitally corrected transposition is a rare congenital anomaly, little is known about the prognosis of patients with this syndrome. The present study evaluated the functional status and clinical course of 73 patients (42 male and 31 female) aged 10 days to 73 years. Follow-up was 1 week to 37 years (mean 12.7 years). Particular attention was paid to the systemic right ventricle, considering the current controversies about long-term right ventricular function. Survival of patients with this condition in general was significantly below normal. The total mortality rate was 11% (8 patients) after a mean follow-up of 12.7 years (range 10 days to 37 years). Mean age at death was 18.5 years (range 6 days to 63 years). The mean age of the survivors at latest follow-up was 21.4 years (range 4 months to 73 years). In most patients, right ventricular function deteriorated and tricuspid valve regurgitation increased, which began at a very young age. Patients without associated lesions developed complications at a higher age compared with the total group. Right ventricular and tricuspid valvular function deteriorated more frequently in patients following intracardiac operation (28% and 52%, respectively) compared with patients undergoing palliative intervention (16%) or no surgery at all (28%). We conclude that survival of patients with this condition is substantially reduced compared with the natural history of an age- and gender-matched general population. This could be explained by the associated cardiac defects, but also by the anatomic condition itself.

Remodeling of the porcine pulmonary autograft wall in the aortic position.

OBJECTIVE: Dilatation and valve regurgitation are disturbing sequelae of the pulmonary root functioning at systemic pressures. We tried to characterize the histologic mode of adaptation of the neoaortic wall. METHODS: We compared routine histologic studies, immunohistochemical staining, and computer-assisted morphometric analysis of aortic, pulmonary autograft, and native pulmonary wall specimens from pigs in which, as a newborn, a valveless pulmonary autograft had been implanted in the aorta. RESULTS: Histologic examination of the pulmonary autograft revealed a viable, normally revascularized wall without degenerative phenomena. Smooth muscle cells were enlarged and rearranged. The characteristic "pulmonary" medial elastin lamellar structure was retained, which was confirmed by morphometry. Immunohistochemistry of the autograft revealed relatively strong staining of type III collagen and alpha smooth muscle actin, exclusive staining of basic fibroblast growth factor, and no staining of proliferation markers proliferating cell nuclear antigen and Ki67. CONCLUSION: The developing pulmonary autograft in the aortic position becomes normally revascularized, lacks major degenerative phenomena, and retains its own typical pulmonary morphologic features. Remodeling is accomplished by increased extracellular matrix deposition with collagen as an important constituent. The marked expression of growth factors in the autograft suggests the persistence of increased metabolic activity.

Decellularization of rat aortic valve allografts reduces leaflet destruction and extracellular matrix remodeling.

OBJECTIVES: Decellularization of aortic valve allografts in advance of transplantation is a promising approach to overcome immune-induced early graft failure. In this study the effects of in vitro cell extraction on extracellular matrix molecules and in vivo remodeling of decellularized aortic valves were investigated in a heterotopic aortic valve rat implantation model. METHODS: Rat aortic valve conduits were decellularized by a 2-step detergent-enzymatic extraction method involving sodium dodecyl sulfate in combination with RNase and DNase. Cellular and acellular allogeneic (2x, n = 4) and syngeneic valve grafts (2x, n = 3) were grafted infrarenally into the descending aorta for 21 days. Immunohistochemical techniques were used to study extracellular matrix constitution (elastin, collagen, fibronectin, and chondroitin sulfate) and cellular infiltration. RESULTS: The decellularization procedure resulted in a complete loss of all cellular structures from the entire valve conduit with minimal damage to the extracellular matrix. All transplanted cellular allografts became deformed, swollen, and acellular with major changes in extracellular matrix structure. The transplanted decellularized allografts, however, retained normal preserved valve leaflets comparable to transplanted cellular and acellular syngeneic grafts. With the exception of cellular syngeneic grafts, all other grafts showed retrovalvular thrombi. CONCLUSIONS: Damage to the valves caused by decellularization technique is much less than the damage caused by the recipient's immune response. In vitro removal of viable cells in (cryopreserved) homografts may decrease graft failure. Seeding with autologous or major histocompatibility complex-matched donor endothelial cells will be necessary to diminish damage induced by an absent blood-tissue barrier.

In situ hybridization: a new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants.

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Brom's three-patch technique for repair of supravalvular aortic stenosis.

OBJECTIVE: Case histories of all patients (n = 29) operated on for supravalvular aortic stenosis from 1962 to the present were reviewed to study different techniques and outcomes. The technique of symmetric aortoplasty with 3 patches (1 in each sinus) is described and compared with other methods. METHODS: Case reports were reviewed and follow-up was completed by contacting the patient's (pediatric) cardiologist. We aimed for a last follow-up visit, including Doppler echocardiographic studies, in a period no more than 12 months earlier than December 1997. Supravalvular aortic stenosis was discrete in 25 and diffuse with involvement of the aortic arch and arch vessels in 4 patients. Additional anomalies were bicuspid aortic valve (n = 5), coarctation (n = 3), ascending aortic aneurysm (n = 1), mitral valve insufficiency (n = 2), pulmonary valvular stenosis (n = 1), and peripheral pulmonary artery stenosis (n = 2). Eleven patients had Williams syndrome and 1 patient had Noonan syndrome. Symmetric aortoplasty with 3 patches (1 in each sinus) was used in 13 patients, whereas other nonsymmetric methods (1, 2, or Y-shaped patches) were used in 16 patients. Mean follow-up was 10.5 years (range: 4 months-36 years). RESULTS: All techniques adequately decreased the pressure gradient. Progression of preoperative aortic valve insufficiency or de novo regurgitation was not observed except in 1 patient in whom the patches inserted were too large. CONCLUSIONS: No difference could be demonstrated in outcome for any surgical technique; however, reconstruction of the aortic root with autologous pericardial patches in each sinus after transection of the aorta has the advantage of symmetry while restoring the normal aortic root anatomy.

Disproportionate enlargement of the pulmonary autograft in the aortic position in the growing pig.

PURPOSE: This study was aimed to demonstrate growth in the pulmonary autograft after transplantation to the aortic position. METHODS AND MATERIALS: In 20 piglets (weight 25.4 +/- 3.5 kg) (mean +/- standard deviation) a Ross operation was performed and in five piglets (weight 9.3 +/- 0.7 kg) (mean +/- standard deviation) the ascending aorta was replaced with a valveless pulmonary autograft. Animals were allowed to grow as much as possible. Postmortem explanted autografts were studied by direct measurements of the valve cusps in the Ross group and of the wall segments in the valveless autograft group. Measurements of the first group were compared with the values of a separate control group, and values of the second group were compared with values of samples taken at operation. RESULTS: In the Ross group, cuspal weight, height, and width increased significantly by comparison with body weight (p < or = 0.003). The rate of increase did not differ significantly from that of the control group with a native pulmonary valve. However, there was a rapid adaptation of the autograft valves resulting in a significantly higher mean cuspal weight, height, and width. In the valveless autograft group, wall circumference, thickness, and height increased significantly (p < or = 0.001). The circumference increased significantly more than that of the native pulmonary wall. Compared with the native aortic wall, the pulmonary autograft media showed retained pulmonary architecture on microscopic study. CONCLUSION: These data suggest that the dimensional increase of the pulmonary autograft in the aortic position in the growing pig is determined by growth and dilatation, that the valve mass increases more than that of the native pulmonary valve, and that the characteristic pulmonary microscopic architecture is retained.

Prime solutions for cardiopulmonary bypass in neonates: antioxidant capacity of prime based on albumin or fresh frozen plasma.

OBJECTIVE: Oxidative damage and inflammation are believed to play an important role in postoperative complications after cardiopulmonary bypass. During bypass, a prime solution with a high antioxidant capacity may reduce the oxidative damage and inflammation. We investigated total antioxidant capacity and individual scavengers during the preparation of 2 different prime solutions. METHODS: The prime solutions were prepared with either pasteurized human albumin or fresh frozen plasma. The total antioxidant capacity was measured with the total radical antioxidant parameter assay and with the ferric-reducing ability of plasma assay. The individual scavengers vitamin C, sulfhydryl groups, uric acid, and total protein were measured before, during, and after the prime preparation. Malondialdehyde was measured as a parameter for lipid peroxidation. RESULTS: Neither prime solution showed a total radical antioxidant parameter value. The ferric-reducing ability of plasma value of prime solutions was lower than that of undiluted human albumin or fresh frozen plasma. Addition of mannitol did not increase the ferric-reducing ability of plasma value. Vitamin C was only found in the fresh frozen plasma prime. Both prime solutions contained sulfhydryl groups and uric acid in low concentrations. During ultrafiltration, low-molecular-weight antioxidants were lost into the ultrafiltrate. CONCLUSIONS: We showed that prime solutions based on either albumin or fresh frozen plasma had very low antioxidant capacity and that ultrafiltration of the prime solution further lowers this capacity. A prime solution with a low antioxidant capacity may increase oxidative stress in neonates undergoing cardiopulmonary bypass.

Pulmonary autograft in ventricular septal defect-aortic insufficiency complex.

Pulmonary autograft aortic root replacement in a child with the ventricular septal defect-aortic insufficiency complex is described. It offers all the advantages of the autograft, avoids closure of the ventricular septal defect, and prevents the use of prosthetic material.